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Theses & Dissertations: Cancer Research

Theses/dissertations from 2024 2024.

Novel Spirocyclic Dimer (SpiD3) Displays Potent Preclinical Effects in Hematological Malignancies , Alexandria Eiken

Chemotherapy-Induced Modulation of Tumor Antigen Presentation , Alaina C. Larson

Understanding the role of MASTL in colon homeostasis and colitis-associated cancer development , Kristina Pravoverov

Dying Right: Supporting Anti-Cancer Therapy Through Immunogenic Cell Death , Elizabeth Schmitz

Therapeutic Effects of BET Protein Inhibition in B-cell Malignancies and Beyond , Audrey L. Smith

Targeting KSR1 to inhibit stemness and therapy resistance , Heidi M. Vieira

Identifying the Molecular Determinants of Lung Metastatic Adaptation in Prostate Cancer , Grace M. Waldron

Identification of Mitotic Phosphatases and Cyclin K as Novel Molecular Targets in Pancreatic Cancer , Yi Xiao

Theses/Dissertations from 2023 2023

Development of Combination Therapy Strategies to Treat Cancer Using Dihydroorotate Dehydrogenase Inhibitors , Nicholas Mullen

Overcoming Resistance Mechanisms to CDK4/6 Inhibitor Treatment Using CDK6-Selective PROTAC , Sarah Truong

Theses/Dissertations from 2022 2022

Omics Analysis in Cancer and Development , Emalie J. Clement

Investigating the Role of Splenic Macrophages in Pancreatic Cancer , Daisy V. Gonzalez

Polymeric Chloroquine in Metastatic Pancreatic Cancer Therapy , Rubayat Islam Khan

Evaluating Targets and Therapeutics for the Treatment of Pancreatic Cancer , Shelby M. Knoche

Characterization of 1,1-Diarylethylene FOXM1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells , Cassie Liu

Novel Mechanisms of Protein Kinase C α Regulation and Function , Xinyue Li

SOX2 Dosage Governs Tumor Cell Identity and Proliferation , Ethan P. Metz

Post-Transcriptional Control of the Epithelial-to-Mesenchymal Transition (EMT) in Ras-Driven Colorectal Cancers , Chaitra Rao

Use of Machine Learning Algorithms and Highly Multiplexed Immunohistochemistry to Perform In-Depth Characterization of Primary Pancreatic Tumors and Metastatic Sites , Krysten Vance

Characterization of Metastatic Cutaneous Squamous Cell Carcinoma in the Immunosuppressed Patient , Megan E. Wackel

Visceral adipose tissue remodeling in pancreatic ductal adenocarcinoma cachexia: the role of activin A signaling , Pauline Xu

Phos-Tag-Based Screens Identify Novel Therapeutic Targets in Ovarian Cancer and Pancreatic Cancer , Renya Zeng

Theses/Dissertations from 2021 2021

Functional Characterization of Cancer-Associated DNA Polymerase ε Variants , Stephanie R. Barbari

Pancreatic Cancer: Novel Therapy, Research Tools, and Educational Outreach , Ayrianne J. Crawford

Apixaban to Prevent Thrombosis in Adult Patients Treated With Asparaginase , Krishna Gundabolu

Molecular Investigation into the Biologic and Prognostic Elements of Peripheral T-cell Lymphoma with Regulators of Tumor Microenvironment Signaling Explored in Model Systems , Tyler Herek

Utilizing Proteolysis-Targeting Chimeras to Target the Transcriptional Cyclin-Dependent Kinases 9 and 12 , Hannah King

Insights into Cutaneous Squamous Cell Carcinoma Pathogenesis and Metastasis Using a Bedside-to-Bench Approach , Marissa Lobl

Development of a MUC16-Targeted Near-Infrared Antibody Probe for Fluorescence-Guided Surgery of Pancreatic Cancer , Madeline T. Olson

FGFR4 glycosylation and processing in cholangiocarcinoma promote cancer signaling , Andrew J. Phillips

Theses/Dissertations from 2020 2020

Cooperativity of CCNE1 and FOXM1 in High-Grade Serous Ovarian Cancer , Lucy Elge

Characterizing the critical role of metabolic and redox homeostasis in colorectal cancer , Danielle Frodyma

Genomic and Transcriptomic Alterations in Metabolic Regulators and Implications for Anti-tumoral Immune Response , Ryan J. King

Dimers of Isatin Derived Spirocyclic NF-κB Inhibitor Exhibit Potent Anticancer Activity by Inducing UPR Mediated Apoptosis , Smit Kour

From Development to Therapy: A Panoramic Approach to Further Our Understanding of Cancer , Brittany Poelaert

The Cellular Origin and Molecular Drivers of Claudin-Low Mammary Cancer , Patrick D. Raedler

Mitochondrial Metabolism as a Therapeutic Target for Pancreatic Cancer , Simon Shin

Development of Fluorescent Hyaluronic Acid Nanoparticles for Intraoperative Tumor Detection , Nicholas E. Wojtynek

Theses/Dissertations from 2019 2019

The role of E3 ubiquitin ligase FBXO9 in normal and malignant hematopoiesis , R. Willow Hynes-Smith

BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response , Kimiko L. Krieger

Targeted Inhibition of Histone Deacetyltransferases for Pancreatic Cancer Therapy , Richard Laschanzky

Human Leukocyte Antigen (HLA) Class I Molecule Components and Amyloid Precursor-Like Protein 2 (APLP2): Roles in Pancreatic Cancer Cell Migration , Bailee Sliker

Theses/Dissertations from 2018 2018

FOXM1 Expression and Contribution to Genomic Instability and Chemoresistance in High-Grade Serous Ovarian Cancer , Carter J. Barger

Overcoming TCF4-Driven BCR Signaling in Diffuse Large B-Cell Lymphoma , Keenan Hartert

Functional Role of Protein Kinase C Alpha in Endometrial Carcinogenesis , Alice Hsu

Functional Signature Ontology-Based Identification and Validation of Novel Therapeutic Targets and Natural Products for the Treatment of Cancer , Beth Neilsen

Elucidating the Roles of Lunatic Fringe in Pancreatic Ductal Adenocarcinoma , Prathamesh Patil

Theses/Dissertations from 2017 2017

Metabolic Reprogramming of Pancreatic Ductal Adenocarcinoma Cells in Response to Chronic Low pH Stress , Jaime Abrego

Understanding the Relationship between TGF-Beta and IGF-1R Signaling in Colorectal Cancer , Katie L. Bailey

The Role of EHD2 in Triple-Negative Breast Cancer Tumorigenesis and Progression , Timothy A. Bielecki

Perturbing anti-apoptotic proteins to develop novel cancer therapies , Jacob Contreras

Role of Ezrin in Colorectal Cancer Cell Survival Regulation , Premila Leiphrakpam

Evaluation of Aminopyrazole Analogs as Cyclin-Dependent Kinase Inhibitors for Colorectal Cancer Therapy , Caroline Robb

Identifying the Role of Janus Kinase 1 in Mammary Gland Development and Breast Cancer , Barbara Swenson

DNMT3A Haploinsufficiency Provokes Hematologic Malignancy of B-Lymphoid, T-Lymphoid, and Myeloid Lineage in Mice , Garland Michael Upchurch

Theses/Dissertations from 2016 2016

EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor , Luke R. Cypher

Inflammation- and Cancer-Associated Neurolymphatic Remodeling and Cachexia in Pancreatic Ductal Adenocarcinoma , Darci M. Fink

Role of CBL-family Ubiquitin Ligases as Critical Negative Regulators of T Cell Activation and Functions , Benjamin Goetz

Exploration into the Functional Impact of MUC1 on the Formation and Regulation of Transcriptional Complexes Containing AP-1 and p53 , Ryan L. Hanson

DNA Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent of Error-Prone Synthesis, and the Role of dNTP Pools , Olga V. Kochenova

Defining the Role of Phosphorylation and Dephosphorylation in the Regulation of Gap Junction Proteins , Hanjun Li

Molecular Mechanisms Regulating MYC and PGC1β Expression in Colon Cancer , Jamie L. McCall

Pancreatic Cancer Invasion of the Lymphatic Vasculature and Contributions of the Tumor Microenvironment: Roles for E-selectin and CXCR4 , Maria M. Steele

Altered Levels of SOX2, and Its Associated Protein Musashi2, Disrupt Critical Cell Functions in Cancer and Embryonic Stem Cells , Erin L. Wuebben

Theses/Dissertations from 2015 2015

Characterization and target identification of non-toxic IKKβ inhibitors for anticancer therapy , Elizabeth Blowers

Effectors of Ras and KSR1 dependent colon tumorigenesis , Binita Das

Characterization of cancer-associated DNA polymerase delta variants , Tony M. Mertz

A Role for EHD Family Endocytic Regulators in Endothelial Biology , Alexandra E. J. Moffitt

Biochemical pathways regulating mammary epithelial cell homeostasis and differentiation , Chandrani Mukhopadhyay

EPACs: epigenetic regulators that affect cell survival in cancer. , Catherine Murari

Role of the C-terminus of the Catalytic Subunit of Translesion Synthesis Polymerase ζ (Zeta) in UV-induced Mutagensis , Hollie M. Siebler

LGR5 Activates TGFbeta Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

LGR5 Activates TGFβ Signaling and Suppresses Metastasis in Colon Cancer , Xiaolin Zhou

Theses/Dissertations from 2014 2014

Genetic dissection of the role of CBL-family ubiquitin ligases and their associated adapters in epidermal growth factor receptor endocytosis , Gulzar Ahmad

Strategies for the identification of chemical probes to study signaling pathways , Jamie Leigh Arnst

Defining the mechanism of signaling through the C-terminus of MUC1 , Roger B. Brown

Targeting telomerase in human pancreatic cancer cells , Katrina Burchett

The identification of KSR1-like molecules in ras-addicted colorectal cancer cells , Drew Gehring

Mechanisms of regulation of AID APOBEC deaminases activity and protection of the genome from promiscuous deamination , Artem Georgievich Lada

Characterization of the DNA-biding properties of human telomeric proteins , Amanda Lakamp-Hawley

Studies on MUC1, p120-catenin, Kaiso: coordinate role of mucins, cell adhesion molecules and cell cycle players in pancreatic cancer , Xiang Liu

Epac interaction with the TGFbeta PKA pathway to regulate cell survival in colon cancer , Meghan Lynn Mendick

Theses/Dissertations from 2013 2013

Deconvolution of the phosphorylation patterns of replication protein A by the DNA damage response to breaks , Kerry D. Brader

Modeling malignant breast cancer occurrence and survival in black and white women , Michael Gleason

The role of dna methyltransferases in myc-induced lymphomagenesis , Ryan A. Hlady

Design and development of inhibitors of CBL (TKB)-protein interactions , Eric A. Kumar

Pancreatic cancer-associated miRNAs : expression, regulation and function , Ashley M. Mohr

Mechanistic studies of mitochondrial outer membrane permeabilization (MOMP) , Xiaming Pang

Novel roles for JAK2/STAT5 signaling in mammary gland development, cancer, and immune dysregulation , Jeffrey Wayne Schmidt

Optimization of therapeutics against lethal pancreatic cancer , Joshua J. Souchek

Theses/Dissertations from 2012 2012

Immune-based novel diagnostic mechanisms for pancreatic cancer , Michael J. Baine

Sox2 associated proteins are essential for cell fate , Jesse Lee Cox

KSR2 regulates cellular proliferation, transformation, and metabolism , Mario R. Fernandez

Discovery of a novel signaling cross-talk between TPX2 and the aurora kinases during mitosis , Jyoti Iyer

Regulation of metabolism by KSR proteins , Paula Jean Klutho

The role of ERK 1/2 signaling in the dna damage-induced G2 , Ryan Kolb

Regulation of the Bcl-2 family network during apoptosis induced by different stimuli , Hernando Lopez

Studies on the role of cullin3 in mitosis , Saili Moghe

Characteristics of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer and Ewing's sarcoma , Haley Louise Capek Peters

Structural and biophysical analysis of a human inosine triphosphate pyrophosphatase polymorphism , Peter David Simone

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Advances in Ovarian Cancer Research: From Biology to Therapeutics

Dear Colleagues,

Recently, substantial progress has been made in treating ovarian cancer, predominantly based on the identification of new molecular targets. For example, PARP inhibitors have been successful largely due to their efficacy in cancers that harbor BRCA mutations or evidence of deficiency in the homologous recombination DNA repair pathway. This collection of articles will address the biological discoveries leading to the next breakthroughs in ovarian cancer research and treatment. Authors are encouraged to submit research studies with translational potential, especially those that include novel biomarkers for treatment effects. This topic thus provides a framework for integrating discoveries at the bench and the bedside.

Dr. Christina M. Annunziata Prof. Dr. Adam R. Karpf Topic Editors

• ovarian cancer
• translational research
• epigenetics
• clinical trials
• tumor biology
• drug discovery

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Ovarian Cancer Treatment Decisions: Accessing Gynecologic Oncology Care

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• March 20, 2019
• Affiliation: Gillings School of Global Public Health, Department of Health Policy and Management
• Ovarian cancer is the most fatal gynecologic malignancy and the fifth leading cause of cancer-related deaths among women in the U.S (USCS 2015). The majority (>80%) of women is diagnosed at late stages (III or IV), often when the prognosis is poor and the 5-year survival rate is 37-45% (Howlader et al. 2015; USCS 2015). Poor prognosis has been attributed to a lack of an early detection strategy, lack of access of specialist care, variations in surgical and chemotherapeutic treatment and patient variability in uptake, as well as healthcare systems characteristics that may contribute to variable quality of care and delays (Bristow et al. 2014b; Carney et al. 2002; Cliby et al. 2015; Thrall et al. 2011). While earlier research efforts have shown treatment from a gynecologic oncologist (GO) to be associated with improved survival, studies have suggested that a substantial number of women with ovarian cancer still do not receive care from a GO at any point during their care (Vernooij et al. 2007). Less is known about when women are accessing the care from a GO (i.e. preoperative/consult only, intraoperatively, postoperatively, or continuous involvement at all phases) and how accessing a GO at different phases of care (i.e. timing) impacts survival. Furthermore, gaps still exist in the literature on the role of a patient’s psychosocial experience and voice in ovarian cancer care (Erwin 2010; Herzog et al. 2014). The overall objective of this research was to understand the effect of timing of GO involvement on mortality (Aim 1 and 2) and explore the patient-level preferences and roles around decision-making and decisional self-efficacy among women with ovarian cancer (Aim 3). Through use of cancer registries supplemented with medical record abstraction (n=2,162) and survey data (n=170), this research examined different aspects around when and where ovarian cancer patients accessed a GO and among those largely seen by a GO, we explored patient-centered factors associated with having greater decisional efficacy and/or decisional support needs. Based on our findings, differences in GO involvement were evident by patient age, race, and place of care. The patient’s perception of a GO as the most important physician in treatment decisions about care did not affect decisional efficacy, but other psychosocial domains did. Though our results likely reflects the confluence of clinical management processes, patient- and provider treatment preferences, and the complexities of the patient-provider clinical interaction that determine the extent of care, it underscores the importance of further examining equitable care delivery to all subgroups of women, particularly those whom may be vulnerable to decisional support needs. We expect that our research findings will help future efforts to identify, understand, and implement interventions to improve receipt of continuous, quality care associated with increased survival and consistent with patient needs.
• decision-making
• Public health
• ovarian cancer
• https://doi.org/10.17615/65y5-z206
• Dissertation
• In Copyright
• Wheeler, Stephanie
• Reeve, Bryce
• Hall, Ingrid
• Brewster, Wendy
• Bennett, Antonia
• Doctor of Philosophy
• University of North Carolina at Chapel Hill Graduate School

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Ovarian Cancer: An Integrated Review

Affiliations.

• 1 Carolina's Medical Center, Charlotte, NC. Electronic address: [email protected].
• 2 Assistant Vice President Patient Care Services, Carolina's Medical Center, Rock Hill, SC.
• 3 Interim Dean, Harris College of Nursing & Health Sciences, Associate Dean for Nursing & Professor, Texas Christian University, Ft Worth, TX.
• PMID: 30867104
• DOI: 10.1016/j.soncn.2019.02.001

Objective: To provide an overview of the risk factors, modifiable and non-modifiable, for ovarian cancer as well as prevention, diagnostic, treatment, and long-term survivorship concerns. This article will also examine current and future clinical trials surrounding ovarian cancer.

Data sources: A review of articles dated 2006-2018 from CINAHL, UpToDate, and National Comprehensive Cancer Network guidelines.

Conclusion: There is no screening test for ovarian cancer and with diagnosis often in the late stages, recurrence is high in this population. Early identification can range from knowing the vague symptoms associated with the cancer to prophylactic surgical removal of at-risk tissue. Standard treatment for ovarian cancer is surgery followed by combination chemotherapy. Although advances are being made, ovarian cancer remains the most fatal female gynecologic cancer.

Implications for nursing practice: Becoming familiar with and educating women about risk factors and the elusive symptoms of ovarian cancer can increase patient autonomy and advocacy, as well as potentially improve patient outcomes for those affected by ovarian cancer.

Keywords: BRCA; gynecologic; oncology; ovarian cancer; prevention; risk factors.

Copyright © 2019 Elsevier Inc. All rights reserved.

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Advances in Ovarian Cancer Research

An ovarian tumor grown in a mouse using human cells. Special techniques were used to create the high-resolution, 3-D view of the cancer’s cell structure and inner workings.

The most common ovarian cancers are those that begin in the epithelial cells that line the fallopian tubes or  ovaries . These, along with cancers that form in the peritoneum , are called epithelial ovarian cancers . Other types of ovarian cancer arise in other cells, including germ cell tumors , which start in the cells that make eggs, and stromal cell tumors , which start in supporting tissues. 

NCI-funded researchers are working to advance our understanding of how to prevent, detect early, and treat ovarian cancer.

This page highlights some of what’s new in the latest research in ovarian cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Prevention of Ovarian Cancer

Women who carry harmful or potentially harmful mutations in the BRCA1 or BRCA2 genes are at increased risk of developing ovarian cancer.  Surgery to remove the ovaries and fallopian tubes in these women is the recommended treatment method and can reduce their lifetime risk of getting ovarian cancer by 95%. However, having this surgery  causes immediate menopause. This may cause health problems if it is much earlier than naturally occurring menopause.

Research has shown that the most common type of ovarian cancer begins in the fallopian tubes , not in the ovaries. This discovery has led doctors to reconsider ways of preventing ovarian cancer.

• Removing fallopian tubes only. An ongoing NCI-sponsored clinical trial is testing whether removing the fallopian tubes but delaying removal of the ovaries will be as effective to reduce the risk of ovarian cancer in women with BRCA1 mutations as removing both the ovaries and fallopian tubes at the same time. This would allow women to maintain premenopausal levels of hormones produced by the ovaries and delay many of the complications associated with menopause.
• Removal of fallopian tubes in people seeking to prevent pregnancy. The discovery that epithelial ovarian cancers most often start in the fallopian tubes has also led to changes in the way some gynecologists approach surgery to prevent pregnancy. Women seeking tubal ligation to prevent pregnancy (often called having your tubes tied) may be offered the option of having their tubes removed instead. Doing so might reduce the possibility of ovarian cancer in the future. 
• Removal of fallopian tubes in people undergoing a hysterectomy. Similarly, some gynecologists recommend that their patients who are undergoing a hysterectomy also have their fallopian tubes removed.
• Testing relatives for gene mutations. NCI is funding efforts to test the relatives of women who have been diagnosed with ovarian cancer in the past.  Researchers are locating women diagnosed with ovarian cancer with the hope to test them and/or their family members for ovarian cancer-related gene mutations. As a result, family members who learn they carry a mutation can take steps to reduce their risk. The overall goal is not only to prevent ovarian cancer, but also to find the best ways to communicate sensitive genetic information to ovarian cancer patients and their family members.

Ovarian Cancer Treatment

Surgery and chemotherapy are the main treatments for ovarian cancer. The location and type of cells where the cancer begins, and whether the cancer is high-grade or low-grade , influences how the cancer is treated. Surgery can cure most people with early-stage ovarian cancer that has not spread beyond the ovaries. For advanced ovarian cancer, the goal of surgery is to remove as much of the cancer as possible, called surgical debulking . 

Platinum-based chemotherapy drugs, such as cisplatin or carboplatin , given in combination with other drugs, such as the targeted therapy bevacizumab (Avastin) , are usually effective in treating epithelial ovarian cancer at any stage. However, in most people with advanced ovarian cancer, the cancer comes back. Treating the cancer again with platinum drugs may work, but eventually the tumors become resistant to these drugs.

Targeted Therapy

Targeted therapy uses drugs or other agents to attack specific types of cancer cells. PARP inhibitors are a type of targeted therapy that can stop a cancer cell from repairing its damaged DNA , causing the cell to die. Cancers in people who have certain mutations in the BRCA genes are considered particularly susceptible to PARP inhibitors. That’s because BRCA genes are involved in the repair of some types of DNA damage, so cancers with BRCA gene alterations already have defects in DNA repair.

The use of PARP inhibitors has transformed treatment for people with advanced epithelial ovarian cancer who have harmful mutations in a BRCA gene. Since the 2014 approval of olaparib (Lynparza) , the first PARP inhibitor to be approved, the number of PARP inhibitors has grown and their uses for people with ovarian cancer have expanded. Now researchers are studying the benefits of combining PARP inhibitors with other drugs.

Clinical trials have shown that using PARP inhibitors as long-term therapy in women with advanced epithelial ovarian cancer delayed progression of the cancer. 

 A different targeted therapy, mirvetuximab soravtansine (Elahere) , is now available to treat women with ovarian cancer that is no longer responding to platinum drugs. FDA recently approved the drug to treat people with platinum-resistant ovarian tumors that produce an excess of a protein called FR-α. Results from a large clinical trial showed that people with this type of ovarian cancer treated with mirvetuximab lived longer overall than people treated with standard chemotherapy .

Treatment after Cancer Progression

Typically, chemotherapy and targeted therapies are stopped once ovarian cancer begins to come back. Clinical trials have shown that where there was more than a 6 month delay between stopping treatment and cancer being found again, resuming the drug bevacizumab (Avastin)  in combination with platinum-based chemotherapy for patients previously treated with bevacizumab  slowed the growth of platinum-sensitive disease . And in women who no longer benefited from platinum-based chemotherapy, non–platinum-based chemotherapy combined with bevacizumab kept the cancer in check longer than chemotherapy alone.

Targeted therapies may also be helpful for people with low-grade ovarian cancer. A trial of the drug trametinib in women with low-grade serous ovarian cancer that had come back showed that it delayed the cancer’s growth compared with treating the cancer with chemotherapy again.

Secondary Surgery

For women with advanced epithelial ovarian cancer that has come back after being in remission, clinical trials have studied the use of secondary surgery or surgery to remove more tumor after the initial surgery with varying results. 

• An NCI-funded phase 3 clinical trial, in patients whose doctor felt that a second surgery could be helpful for treating the cancer, found that secondary surgery followed by chemotherapy did not increase overall survival compared with chemotherapy alone. Of the studies listed, this one reflected the most likely scenario in real-world practice.
• A trial done in China studied a group of patients more likely to benefit from the intervention. The trial tested secondary surgery followed by chemotherapy and did show improvements in how long women with recurrent epithelial ovarian cancer lived without their cancer growing .
• In a third trial, conducted in Europe, researchers identified people with recurrent ovarian cancer who were most likely to benefit from surgery. They found that women who had secondary surgery followed by chemotherapy lived an average of nearly 8 months longer than women who only received chemotherapy.

In the Chinese and European trials, and in an analysis of 64 clinical trials and other studies , the benefits of secondary surgery were observed only in women who had all of their visible cancer removed.

NCI-Supported Research Programs

Many NCI-funded researchers at the National Institutes of Health campus, and across the United States and the world, are seeking ways to address ovarian cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of ovarian cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes.

The Women’s Malignancies Branch in NCI’s Center for Cancer Research conducts basic and clinical research in breast and gynecologic cancers, including early-phase clinical trials at the NIH Clinical Center in Bethesda, Maryland. 

The Ovarian Specialized Programs of Research Excellence (SPOREs) promote collaborative translational cancer research. This group works to improve prevention and treatment approaches, along with molecular diagnostics , in the clinical setting to help people with ovarian cancer.

The Ovarian Cancer Cohort Consortium , part of the NCI Cohort Consortium, is an international consortium of more than 20 cohort studies that follow people with ovarian cancer to improve understanding of ovarian cancer risk, early detection, tumor differences, and prognosis. 

NCI’s clinical trials programs, the National Clinical Trials Network , Experimental Therapeutics Clinical Trials Network , and NCI Community Oncology Research Program , all conduct or sponsor clinical studies of ovarian cancer.

Clinical Trials for Ovarian Cancer

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for the treatment of ovarian cancer.

Ovarian Cancer Research Results

The following are some of our latest news articles on ovarian cancer research:

Approval of Elahere Expands Treatment Options for Some Advanced Ovarian Cancers

Implanted “Drug Factories” Deliver Cancer Treatment Directly to Tumors

Trametinib Is a New Treatment Option for Rare Form of Ovarian Cancer

When Ovarian Cancer Returns, Surgery May Be a Good Choice for Selected Patients

How Does Ovarian Cancer Form? A New Study Points to MicroRNA

Ovarian Cancer Studies Aim to Reduce Racial Disparities, Improve Outcomes

View the full list of Ovarian Cancer Research Results and Study Updates .

Journal of Ovarian Research

Call for papers: microbiome in reproductive health, dysfunction, and cancer.

Edited by: Professor Julang Li, PhD , University of Guelph, Canada Svetlana Madjunkova, MD, PHD , CReATe Fertility Centre, Canada Professor Ofer Reizes, MD, PhD , Cleveland Clinic, United States of America Submission Status: Open until 1 May 2025

Call for Papers: Nanotechnological Approaches for the Treatment of Ovarian Cancer

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The molecular prognostic score, a classifier for risk stratification of high-grade serous ovarian cancer

Authors: Siddik Sarkar, Sarbar Ali Saha, Abhishek Swarnakar, Arnab Chakrabarty, Avipsa Dey, Poulomi Sarkar, Sarthak Banerjee and Pralay Mitra

Drug-free in vitro activation combined with ADSCs-derived exosomes restores ovarian function of rats with premature ovarian insufficiency

Authors: Qian Li, Zhiqiang Zhang, Wenxin Shi, Zhongkang Li, Yanlai Xiao, Jingkun Zhang and Xianghua Huang

Effects of licorice extract in combination with a low-calorie diet on obesity indices, glycemic indices, and lipid profiles in overweight/obese women with polycystic ovary syndrome (PCOS): a randomized, double-blind, placebo-controlled trial

Authors: Hadis Hooshmandi, Akram Ghadiri-Anari, Ali Mohammad Ranjbar, Hossein Fallahzadeh, Mahdieh Hosseinzadeh and Azadeh Nadjarzadeh

Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation

Authors: Riya Khetan, Preethi Eldi, Noor A. Lokman, Carmela Ricciardelli, Martin K. Oehler, Anton Blencowe, Sanjay Garg, Katherine Pillman and Hugo Albrecht

Effects of mind-body interventions on polycystic ovary syndrome: a comprehensive meta-analysis

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Possibility of live birth in patients with low serum β-hCG 14 days after blastocyst transfer

Authors: Yixuan Wu and Haiying Liu

Role of CA125 in predicting ovarian cancer survival - a review of the epidemiological literature

Authors: Digant Gupta and Christopher G Lis

A combination of spearmint and flaxseed extract improved endocrine and histomorphology of ovary in experimental PCOS

Authors: Mina Mehraban, Gholamali Jelodar and Farhad Rahmanifar

Rising serum CA-125 levels within the normal range is strongly associated recurrence risk and survival of ovarian cancer

Authors: Szymon Piatek, Grzegorz Panek, Zbigniew Lewandowski, Mariusz Bidzinski, Dominika Piatek, Przemyslaw Kosinski and Miroslaw Wielgos

Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review

Authors: Vincent Dochez, Hélène Caillon, Edouard Vaucel, Jérôme Dimet, Norbert Winer and Guillaume Ducarme

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Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.

Topical areas include, but are not restricted to:

• Ovary development, hormone secretion and regulation
• Follicle growth and ovulation
• Infertility and Polycystic ovarian syndrome
• Regulation of pituitary and other biological functions by ovarian hormones
• Ovarian cancer, its prevention, diagnosis and treatment
• Drug development and screening
• Role of stem cells in ovary development and function

Featured Article Collection: Extracellular vesicles

Join us in commemorating World Ovarian Cancer Day on May 8th with a look back at the most influential articles published in  Journal of Ovarian Research on ovarian cancer in the last few years. 

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Ovarian cancer articles from across Nature Portfolio

Ovarian cancer is an abnormal cell growth (tumour) arising in the ovary. The majority of ovarian cancers are epithelial and develop in women over 50. Screening is highly recommended in women with a family history of ovarian cancer.

Latest Research and Reviews

Proteomic landscape of epithelial ovarian cancer

It remains essential to find clinically relevant biomarkers in epithelial ovarian cancer (EOC). Here, the authors perform a comprehensive proteomic profiling of tissue and plasma samples from EOC and control patients; they find potential biomarkers for EOC early detection and develop methods for tumour recurrence prediction.

• Liujia Qian
• Jianqing Zhu
• Tiannan Guo

Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer

• Kristen R. Ibanez
• Duncan Donohue
• Jung-Min Lee

Large-scale proteomics reveals precise biomarkers for detection of ovarian cancer in symptomatic women

• Emma Ivansson
• Julia Hedlund Lindberg
• Stefan Enroth

Spatial tumor immune microenvironment phenotypes in ovarian cancer

• Claudia Mateiou
• Lavanya Lokhande
• Anna Gerdtsson

Timing of whole genome duplication is associated with tumor-specific MHC-II depletion in serous ovarian cancer

There is high prevalence of whole genome duplication (WGD) in high grade serous ovarian cancer. Here, the authors compare tumours with and without WGD and find that those that acquired WGD early during tumour evolution are associated with worse survival and have the lowest expression of MHC-II.

• Nikki L. Burdett
• Madelynne O. Willis
• Elizabeth L. Christie

Pre-diagnosis tea and coffee consumption and survival after a diagnosis of ovarian cancer: results from the Ovarian Cancer Association Consortium

• Christina M. Nagle
• Torukiri I. Ibiebele
• Penelope M. Webb

News and Comment

Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer.

• Diana Romero

Mirvetuximab soravtansine superior to chemotherapy in platinum-resistant epithelial ovarian cancer

• Peter Sidaway

A medley of resistance in ovarian cancers

Multi-omic profiling of lesions at autopsy reveals a plethora of resistance mechanisms present within individual patients with ovarian cancer. This highlights the extreme challenge faced in treating end-stage disease and underscores the need for new methods of early detection and intervention.

• Barbara Hernando
• Geoff Macintyre

A biomarker-driven therapy for ovarian cancer

An antibody–drug conjugate showed impressive anti-cancer activity in selected patients with platinum-resistant ovarian cancer, and could become a new standard of care.

• Karen O’Leary

Beating the odds: molecular characteristics of long-term survivors of ovarian cancer

High-grade serous ovarian cancer, the most common form of the disease, is often fatal. This study investigated the genomic and immune characteristics of tumors from women who survived more than 10 years after their initial diagnosis, and compared them with short-term and moderate-term survivors.

Cytoreductive surgery effective after relapse

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Ovarian Cancers: Evolving Paradigms in Research and Care (2016)

Chapter: 1 introduction and background.

Introduction and Background

Although recent years have seen many promising advances in cancer research, there remain surprising gaps in the fundamental knowledge about and understanding of ovarian cancer. Researchers now know that ovarian cancer, like many other types of cancer, should not be thought of as a single disease; instead, several distinct subtypes exist with different origins, different risk factors, different genetic mutations, different biological behaviors, and different prognoses, and much remains to be learned about them. For example, researchers do not have definitive knowledge of exactly where these various ovarian cancers originate and how they develop. Such unanswered questions have impeded progress in the prevention, early detection, treatment, and management of ovarian cancers. In particular, the failure to achieve major reductions in ovarian cancer morbidity and mortality during the past several decades is likely due to several factors, including

• A lack of research focusing on specific disease subtypes;
• An incomplete understanding of genetic and nongenetic risk factors;
• An inability to develop and validate effective screening and early detection tools;
• Inconsistency in the delivery of the standard of care;
• Limited evidence-based personalized medicine approaches tailored to the disease subtypes and other tumor characteristics; and
• Limited attention paid to research on survivorship issues, including supportive care with long-term management of active disease.

The symptoms of ovarian cancers can be nonspecific and are often not seen as indicating a serious illness by women or their health care providers until the symptoms worsen, at which point the cancer may be widespread and difficult to cure. The fact that these cancers are not diagnosed in many women until they are at an advanced stage is a major factor contributing to the high mortality rate for ovarian cancer, especially for women with high-grade serous carcinoma (HGSC)—the most common and lethal subtype. Indeed, roughly two-thirds of women with ovarian cancer are diagnosed with an advanced-stage cancer or with a cancer that has not been definitively staged, and the 5-year survival rate for these women is less than 30 percent (Howlader et al., 2015). Although many ovarian cancers respond well to initial treatment, including the surgical removal of grossly visible tumor (cytoreduction) and chemotherapy, the vast majority of the tumors recur. Recurrent ovarian cancers may again respond to further treatment, but virtually all of them will ultimately become resistant to current drug therapies.

Finally, less emphasis has been placed on research that focuses on how to improve therapeutic interventions by subtype or on how to reduce the morbidity of ovarian cancers. Little emphasis has been placed on understanding survivorship issues and the supportive care needs of women with ovarian cancer, including management of the physical side effects of treatment (including both initial and chronic, ongoing therapies) and addressing the psychosocial effects of diagnosis and treatment. The lasting impact of a diagnosis of ovarian cancer and its related treatment can be significant both for the women who experience recurrent disease and for the women who experience long (or indefinite) periods of remission. This report gives an overview of the state of the science in ovarian cancer research, highlights the major gaps in knowledge in that field, and provides recommendations that might help reduce the incidence of and morbidity and mortality from ovarian cancers by focusing on promising research themes and technologies that could advance risk prediction, early detection, comprehensive care, and cure.

STUDY CHARGE AND APPROACH

In spite of their high mortality rates, ovarian cancers often do not receive as much attention as other cancers. In part, this is because ovarian cancers are relatively uncommon. Furthermore, ovarian cancer has been called a “silent killer” because researchers once believed that there were no perceptible symptoms in the earlier stages of the disease (Goff, 2012). However, more recent research has shown that most women diagnosed with ovarian cancer report symptoms such as bloating, pelvic or abdominal pain, and urinary symptoms, and many women recall having these symptoms

for an extended period of time before diagnosis (Goff et al., 2000, 2004). Often, due to the nonspecific nature of ovarian cancer symptoms, patients and physicians do not recognize these early symptoms as indicative of ovarian cancer (Gajjar et al., 2012; Jones et al., 2010; Lockwood-Rayermann et al., 2009).

In this context, in 2006 the U.S. Congress passed the Gynecologic Cancer Education and Awareness Act of 2005, 1 which amended the Public Health Service Act (42 U.S.C. 247b-17) to direct the secretary of the U.S. Department of Health and Human Services to launch a campaign to “increase the awareness and knowledge of health care providers and women with respect to gynecologic cancers.” The law is commonly known as Johanna’s Law in memory of Johanna Silver Gordon, a public school teacher from Michigan who died from late-stage ovarian cancer (Twombly, 2007). The law was reauthorized in 2010, 2 and, as part of the Consolidated Appropriations Act of 2014, Congress directed the Centers for Disease Control and Prevention (CDC) to use funds from Johanna’s Law to perform a review of the state of the science in ovarian cancer. 3

Study Charge

In the fall of 2014, with support from the CDC, the Institute of Medicine (IOM) formed the Committee on the State of the Science in Ovarian Cancer Research to examine and summarize the state of the science in ovarian cancer research, to identify key gaps in the evidence base and challenges to addressing those gaps, and to consider opportunities for advancing ovarian cancer research (see Box 1-1 ). The committee determined that the best way to facilitate progress in reducing morbidity and mortality would be to identify the research gaps that were most salient and that, if addressed, could affect the greatest number of women.

The committee was also asked to consider ways to translate and disseminate new findings and to communicate these findings to all stakeholders. This report, therefore, not only describes evidence-based approaches to translation and dissemination, but it also suggests strategies for communicating those approaches.

________________

1 Gynecologic Cancer Education and Awareness Act of 2005, Public Law 475, 109th Cong., 2nd sess. (January 12, 2007).

2 To reauthorize and enhance Johanna’s Law to increase public awareness and knowledge with respect to gynecologic cancers, Public Law 324, 111th Cong., 2nd sess. (December 22, 2010).

3 Explanatory statement submitted by Mr. Rogers of Kentucky, Chairman of the House Committee on Appropriations regarding the House amendment to the Senate amendment on H.R. 3547, consolidated... , 113th Cong., 2nd sess., Congressional Record 160, no. 9, daily ed. (January 15, 2014):H 1035.

BOX 1-1 Statement of Task

An ad hoc committee under the auspices of the Institute of Medicine will review the state of the science in ovarian cancer research and formulate recommendations for action to advance the field. The committee will:

• Summarize and examine the state of the science in ovarian cancer research;
• Identify key gaps in the evidence base and the challenges to addressing those gaps;
• Consider opportunities for advancing ovarian cancer research; and
• Examine avenues for translation and dissemination of new findings and communication of new information to patients and others.

The committee will make recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of and morbidity and mortality from ovarian cancer.

The committee emphasizes that its charge was to focus on research in ovarian cancer and, particularly, to focus on the gaps in the evidence base that, if addressed, would have the greatest impact on the lives of women diagnosed with or at risk for ovarian cancer. The committee did not explore issues affecting the care of women with ovarian cancer (e.g., health insurance coverage and policy issues) in depth. For example, while the regulatory process for drug approval is interconnected with the clinical trial enterprise (e.g., the design of clinical trials may determine what data are gathered and, in turn, affect the approval process), a full examination of issues related to the approval of new drugs was beyond the scope of this report. Furthermore, it was outside the scope of this report to fully evaluate specific research programs in ovarian cancer. In addition, this report does not offer an exhaustive cataloguing of every actor engaged in ovarian cancer research, nor does it detail every effort made by stakeholders to engage in dissemination and implementation efforts. Rather, the examples given in this report are meant to highlight the efforts being made, recognizing there are many other similar efforts.

Finally, the committee focused as much as possible on the research gaps and the challenges to addressing those gaps that are unique to ovarian cancer. However, those research gaps and challenges that are common to all types of cancer research, or even to all health care research, are described as appropriate. For example, while the clinical trials system is extremely important to the ovarian cancer research enterprise, many of the outstanding

questions and concerns related to the clinical trials system are shared with all types of cancer research and could not be explored or discussed in detail. Therefore, the committee turned to previous IOM reports specific to the clinical trials system in general for guidance, and then considered aspects of the system that are particularly relevant for ovarian cancer research.

Study Approach

The study committee included 15 members with expertise in ovarian cancer, gynecologic oncology, gynecologic pathology, gynecologic surgery, molecular biology, cancer genetics and genomics, genetic counseling, cancer epidemiology, immunology, biostatistics, bioethics, advocacy, survivorship, and health communication. (See Appendix E for biographies of the committee members.)

A variety of sources informed the committee’s work. The committee met in person four times, and during two of those meetings it held public sessions to obtain input from a broad range of relevant stakeholders. In addition, the committee conducted extensive literature reviews, reached out to a variety of public and private stakeholders, and commissioned one paper.

The committee encountered a number of challenges. In some cases, it found itself limited by what was available in the published literature. At other times, it was challenged by the use of different methodologies for the classification of ovarian cancers in the research literature. For instance, many studies in the literature consolidate all types of ovarian cancer instead of studying and reporting them by subtype. In its review of the evidence, the committee discerns, where possible, whether the reported findings apply to ovarian cancers as a whole or to particular subtypes. One other major challenge to reviewing and summarizing the evidence base on ovarian cancer, particularly in summarizing the epidemiology by subtype, was the way that the grading, classification, and nomenclature for ovarian cancers have varied over the years.

In order to guide its deliberative process, the committee chose to make recommendations about research gaps based on the continuum of cancer care (see Figure 1-1 ). The committee focused on cross-cutting research areas critical to each phase of the continuum: the basic biology of ovarian cancers, innovative clinical trial design, intervention development, methods to reduce practice-related disparities, and supportive care research and practice. Finally, the committee considered evidence and strategies for the dissemination and implementation of knowledge across all of these domains.

DEFINITIONS OF KEY TERMS

This section provides definitions of several key terms that are relevant to this report, and also provides an explanation of how the committee

FIGURE 1-1 Framework for research in ovarian cancer. NOTE: Colored figures represent phases of the ovarian cancer care continuum where research can be focused. Black boxes indicate critical areas of ongoing cross-cutting research that span these phases.

selected terms for consistency throughout the report. A glossary including more terms is provided in Appendix B , and a list of key acronyms is included in Appendix A .

Target Population

This report is concerned with women with ovarian cancers. However, the committee recognizes that there is a small subpopulation of transgender men who may be at risk for ovarian cancers, particularly due to the use of testosterone therapy (Dizon et al., 2006; Hage et al., 2000).

Basic Cancer Terminology

The terms “cancer,” “carcinoma,” and “tumor” can be confused or interchanged at times. Cancer is “a term for diseases in which abnormal cells divide without control and can invade nearby tissues,” while a tumor (which can be cancerous or noncancerous) is “an abnormal mass of tissue that results when cells divide more than they should or do not die when they should” (NCI, 2015d). Carcinomas are cancers that “begin in the skin or in tissues that line or cover internal organs” (i.e., arising from epithelial cells) (NCI, 2015d). As was noted previously, this report focuses on ovarian carcinomas, because they are the most common and most lethal of the ovarian cancer subtypes.

While the committee endeavored to focus on carcinomas wherever possible, there were times when that was not possible, and the terms “cancer” and “tumor” are used when appropriate. For example, many studies are based on ovarian cancers collectively and do not analyze data based on the subtypes. The committee also uses the term “tumor” when discussing the physical mass itself. Finally, although the term “ovarian cancer” technically represents an array of disease subtypes, the committee refers to the disease in the plural form (i.e., “ovarian cancers”) whenever appropriate in order to emphasize the heterogeneity of the disease and all its subtypes.

When ovarian cancer reappears in a woman, it is usually referred to as “relapsed” or “recurrent” disease. The National Cancer Institute (NCI) defines cancer recurrence as “cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body” (NCI, 2015d). Noting that a cancer that has recurred is also called “relapsed cancer,” the NCI defines relapse as “the return of a disease or the signs and symptoms of a disease after a period of improvement.” In this report, for consistency the committee uses only the terms “recurrent” or “recurrence”—and not “relapsed” or “relapse”—but

it recognizes that there may be subtle differences, preferences, or interpretations in the use of the two terms.

DEFINING AND CLASSIFYING OVARIAN CANCERS

“Ovarian cancer” is a generic term that can be used for any cancer involving the ovaries. The ovaries are composed of several different cell types, including the germ cells, specialized gonadal stromal cells (e.g., granulosa cells, theca cells, Leydig cells, and fibroblasts), and epithelial cells; ovarian cancers can arise from any of these cell types. Ovarian cancers with epithelial differentiation (carcinomas) account for more than 85 percent of ovarian cancers and are responsible for most ovarian cancer–related deaths (Berek and Bast, 2003; Braicu et al., 2011; SEER Program, 2015; Seidman et al., 2004). Consequently, this report will focus on the biology of ovarian carcinomas, while recognizing that although other, less common types of ovarian malignancies do exist, they are responsible for a smaller fraction of ovarian cancer–related deaths.

As with ovarian cancers in general, ovarian carcinomas are quite heterogeneous and come in a variety of different tumor types (see Figure 1-2 ). The major ovarian carcinoma subtypes are named according to how closely the tumor cells resemble normal cells lining different organs in the female genitourinary tract. Specifically, serous, endometrioid, and a subset

FIGURE 1-2 Percentage of cases by major ovarian carcinoma subtype. NOTE: Other* refers to mixed or transitional carcinomas where it is not possible to categorize to a single subtype. SOURCE: Gilks et al., 2008; Seidman et al., 2003, 2004.

of mucinous carcinomas exhibit morphological features that are similar to normal epithelial cells in the fallopian tube, endometrium, and endocervix, respectively. Furthermore, clear cell carcinomas resemble cells seen in the gestational endometrium (Scully et al., 1999).

Over the past several years, researchers have developed a streamlined classification scheme in which the majority of ovarian carcinomas can be divided into five types:

• Endometrioid carcinoma (EC),
• Clear cell carcinoma (CCC),
• Low-grade serous carcinoma (LGSC), and
• Mucinous carcinoma (MC) (Gurung et al., 2013; Kalloger et al., 2011).

Some researchers have offered an even simpler classification with a scheme in which ovarian carcinomas are divided into Type I and Type II tumors based on shared features (Shih and Kurman, 2004). In this scheme, Type I carcinomas are low-grade, relatively unaggressive, and genetically stable tumors that often arise from recognizable precursor lesions such as endometriosis or benign tumors and frequently harbor somatic mutations that deregulate specific cell signaling pathways or chromatin remodeling complexes. ECs, CCCs, MCs, and LGSCs are considered Type I tumors and are often characterized by KRAS, BRAF , or PTEN mutations. Type II carcinomas are high-grade, biologically aggressive tumors from their inception, with a propensity for metastasis from small, even microscopic, primary lesions. HGSCs represent the majority of Type II tumors and are characterized by the mutation of TP53 and frequent mutations of genes (e.g., BRCA1 and BRCA2 ) that lead to homologous recombination defects (Pennington et al., 2014).

Because the data collected thus far provide compelling evidence that each of the various Type I tumors has distinct biological and molecular features, these tumors will be referred to by their specific histologic type throughout the remainder of this report. However, the Type I and Type II terminology will be used where necessary, most often in referring to studies conducted using this classification scheme. Furthermore, because the majority of ovarian carcinomas are HGSCs, and HGSCs are the subtype with the worst prognosis, this report will primarily focus on this subtype. When referring to historical or large-scale epidemiologic studies of ovarian cancer for which the tumor subtypes were not specified, readers can reasonably assume that most of the tumors were HGSCs.

After being classified by subtype, tumors are usually also assigned a grade, based on how closely the tumor cells resemble their normal counter-

parts. Both two-grade and three-grade systems have been applied in various situations; in both types of systems, the lower-grade tumors more closely resemble normal cells than the higher-grade tumors (Malpica et al., 2004; Silverberg, 2000).

OVARIAN CANCER PATTERNS AND DEMOGRAPHICS 4

Although ovarian cancer is relatively rare, it is one of the deadliest cancers. It was estimated that more than 21,000 women in the United States would receive a diagnosis of an ovarian cancer in the year 2015 5 (Howlader et al., 2015). This represents almost 12 new cases for every 100,000 women and 2.6 percent of all new cancer cases in women in the United States. Nearly 200,000 women in the United States are living with ovarian cancer in any given year, and approximately 1.3 percent of all American women will be diagnosed with ovarian cancer at some point in their lives, which qualifies ovarian cancer as a rare disease as defined by the National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (NIH, 2015a). Still, according to estimates, more than 14,000 American women will have died from ovarian cancer in 2015, which corresponds to approximately 7.7 deaths per 100,000 women and 5.1 percent of all cancer deaths among American women (ACS, 2015; Howlader et al., 2015). Despite its relatively low incidence, ovarian cancer is the fifth leading cause of cancer deaths among U.S. women and the eighth leading cause of women’s cancer deaths worldwide (Ferlay et al., 2015; Howlader et al., 2015). By comparison, breast cancer is more common—among American women the estimated number of new cases of breast cancer each year is 10 times the number of new cases of ovarian cancer—but ovarian cancer is more deadly, with a death-to-incidence ratio that is more than three times higher than for breast cancer (Howlader et al., 2015) (see Figure 1-3 ).

The survival rate for ovarian cancer is quite low. For 2005 to 2011, the 5-year survival rate in the United States was just 45.6 percent. By contrast, the 5-year survival rate in the United States for the same period was nearly 90 percent for breast cancer, more than 80 percent for endometrial cancer, and nearly 70 percent for cervical cancer. However, given the typical course of initial remission and subsequent recurrence for women with ovarian cancer, the 5-year survival metric may not reflect the overall disease course. At advanced stages, MCs and CCCs in particular have poorer prognoses and survival rates than other carcinoma subtypes (Mackay et al., 2010).

4 Terminology to describe race and ethnicity reflects the terminology used in the original sources.

5 Because historical epidemiologic data typically combine the multiple types of ovarian cancer, they are discussed as a single disease in this discussion of epidemiology.

FIGURE 1-3 The ratio between the death and incidence rates for ovarian, breast, endometrial, and cervical cancers per 100,000 women in the United States, 2008–2012. SOURCE: Howlader et al., 2015.

The incidence of ovarian cancer has declined slightly since the mid-1970s, when the incidence was approximately 16 new cases per 100,000 women (Howlader et al., 2015). Mortality from ovarian cancer has also declined—from 9.8 deaths per 100,000 women in 1975 to 7.4 deaths per 100,000 women in 2012. However, the decline in mortality is relatively small when compared to reductions in death rates achieved for most other female gynecological cancers and for breast cancer in women. For example, the death rate from breast cancer fell by one-third between 1975 and 2012, from 31.4 deaths per 100,000 women to 21.3 deaths per 100,000, and the death rate from cervical cancer dropped by more than half during that same period, from 5.6 deaths per 100,000 women to 2.3 deaths per 100,000.

Among women who were diagnosed with ovarian cancer between 1975 and 1977, only 36 percent lived 5 years or more, while nearly half (46 percent) of women diagnosed with ovarian cancer between 2005 and 2007 lived at least 5 years beyond their diagnosis (Howlader et al., 2015). However, that improvement in survival rates was driven primarily by improvements in survival among white women; survival rates decreased (from 42 to 36 percent) over the same period for black women (ACS, 2015; also see section Race and Ethnicity later in this chapter).

Stage Distribution

Ovarian cancer’s high mortality and low survival rates can be attributed in part to the fact that it is rarely diagnosed at an early stage. Indeed, 60 percent of women are diagnosed with advanced disease, when the cancer has already spread beyond the ovary to distant organs or lymph nodes (Howlader et al., 2015). In comparison, as seen in Figure 1-4 , other female cancers are more commonly diagnosed during the localized or regional stages.

The relatively late stage of diagnosis for ovarian cancer is particularly important because survival is highly correlated with the stage at diagnosis (see Figure 1-5 ). While the 5-year survival rate is 45.6 percent overall, it is substantially higher for women diagnosed while the cancer is still at the localized stage (92.1 percent) or the regional stage (73.2 percent), and it is substantially lower for women diagnosed at the distant stage (28.3 percent) (ACS, 2015; Howlader et al., 2015). Survival is lowest among women who receive an unstaged ovarian cancer diagnosis (22.9 percent).

White and black women show similar patterns of stage distribution (see Figure 1-6 ). However, there is a difference in stage of diagnosis in women

FIGURE 1-4 Distribution (percentage) of stage of diagnosis for cancers of the breast, endometrium, cervix, and ovary among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

FIGURE 1-5 Five-year relative survival (percentage) from ovarian cancer by stage at diagnosis among U.S. women, 2005–2011. SOURCE: Howlader et al., 2015.

FIGURE 1-6 Stage distribution (percentage of cases) at diagnosis among white and black U.S. women diagnosed with ovarian cancer, 2003–2009. SOURCE: Howlader et al., 2015.

of different ages, with women younger than age 65 tending to be diagnosed at earlier stages than women older than age 65 (see Figure 1-7 ).

Ovarian cancer incidence increases with age, with a sharp increase in the rate beginning in the mid-40s (see Figure 1-8 ). From 2008 to 2012, nearly 88 percent of all new cases of ovarian cancer occurred among women ages 45 and older, with 69 percent of cases among women ages 55 and older, and the average age at diagnosis was 63 years. A half-century ago, most cases occurred among women between the ages of 35 and 63, and the average age at diagnosis was 48.5 years (Munnell, 1952).While the age-adjusted incidence rate for ovarian cancer among all women is nearly 12 cases per 100,000 women, the rate varies sharply with age, with women younger than age 65 having an incidence rate of 7.5 cases per 100,000 women while women 65 years old and older have an incidence rate of more than 42 cases per 100,000 women (Howlader et al., 2015).

Mortality rates also increase sharply with age. The death rate for women aged 65 and older is approximately 13 times that of women less than age 65 (see Figure 1-9 ). Furthermore, while mortality rates have de-

FIGURE 1-7 Stage distribution (percentage of cases) at diagnosis among women diagnosed with ovarian cancer by age, 2003–2009. SOURCE: Howlader et al., 2015.

FIGURE 1-8 Age-adjusted incidence of ovarian cancer per 100,000 women in the United States by age group. SOURCE: SEER Program, 2015.

FIGURE 1-9 Trends in age-adjusted death rates from ovarian cancer per 100,000 women in the United States by age group, 1975–2012. SOURCE: Howlader et al., 2015.

clined overall in the past 40 years, most of this decline is attributable to decreases in mortality among women diagnosed with ovarian cancer less than age 65 (ACS, 2015; Howlader et al., 2015).

Race and Ethnicity

The patterns of ovarian cancer incidence and mortality differ substantially among women of different races and ethnic backgrounds (see Figure 1-10 ). Whites have the highest incidence of ovarian cancer, followed by Hispanics, American Indian/Alaska Natives, blacks, and Asian/Pacific Islanders (ACS, 2015; Howlader et al., 2015; Singh et al., 2014). The 5-year survival rate is highest among Asian/Pacific Islanders, followed by Hispanics, whites, American Indian/Alaska Natives, and blacks, while mortality rates are highest among whites, followed by blacks, Hispanics, American Indian/Alaska Natives, and Asian/Pacific Islanders. A particularly dramatic contrast can be seen between black and Asian/Pacific Islander women. While the two groups are similar in having low incidence rates, black women have the second-highest mortality rates and the lowest survival rates, while Asian/Pacific Islanders have the lowest mortality and the highest survival rates. The incidence of ovarian cancer, particularly HGSC, is higher than average in women of Ashkenazi Jewish ancestry, in part because of the higher prevalence of deleterious mutations in cancer-predisposition genes such as BRCA1 and BRCA2 among these women (ACS, 2015; Moslehi et al., 2000).

FIGURE 1-10 Age-adjusted ovarian cancer incidence and mortality per 100,000 U.S. women by race and ethnicity, 2008–2012. SOURCE: Howlader et al., 2015.

Furthermore, the variations in the incidence rates of ovarian cancer by race and ethnicity change as women age (see Figure 1-11 ). For example, whites and Asian/Pacific Islanders have similar incidence rates until around age 50, when their incidence rates begin to diverge. White women aged 45–49 have an age-specific incidence rate of 15.1 cases per 100,000, and Asian/Pacific Islanders of the same age group have a very similar rate of 15.5 cases per 100,000. By contrast, white women aged 80–84 have an incidence rate of 50.8 cases per 100,000, while Asian/Pacific Islanders of the same age group have a dramatically lower rate of 30.1 cases per 100,000.

Historical trends also show considerable variations by race. Between 2003 and 2012, mortality rates decreased significantly among whites and Hispanics, while declines in mortality among blacks, Asian/Pacific Island-

FIGURE 1-11 Age-specific incidence rates of ovarian cancer per 100,000 women in the United States by race/ethnicity and age at diagnosis, 2008–2012. NOTE: Rates for American Indian/Alaska Natives are only displayed for ages 50 through age 69, because the number of cases in other age groups were less than 16 per age group. SOURCE: SEER Program, 2015.

ers, and American Indian/Alaskan Natives were not statistically significant (Howlader et al., 2015). Moreover, while survival rates have increased among women overall and among white women since the mid-1970s, survival rates have declined slightly among black women (see Figure 1-12 ). Furthermore, although black women had higher rates of survival compared to white women and to women overall in 1975, by the mid-1980s survival rates had begun to reverse, such that black women now have lower survival rates than white women and women of all races overall even despite gains in survival among blacks in the 1990s (ACS, 2015).

In the United States, there are slight geographic variations in ovarian cancer incidence, but these variations are not significant (Howlader et al., 2015; Ries et al., 2007). However, the differences in mortality from state to state are significant. In the United States, from 2008 to 2012 the death rate for ovarian cancer was 7.7 deaths per 100,000 women. During that same period, the age-adjusted death rates by state ranged from a low of 5.3 deaths per 100,000 women in Hawaii to a high of 9.0 deaths per 100,000 women in Oregon (Howlader et al., 2015). Despite the wide variation

FIGURE 1-12 Trends in 5-year relative survival rates (percentage) for ovarian cancer among U.S. women by race, 1975–2011. SOURCE: Howlader et al., 2015.

across the states, only Alabama, Oregon, Pennsylvania, and Washington have significantly higher rates, statistically speaking, than the United States as a whole, while only Florida, Hawaii, and Texas have significantly lower rates than the national average.

Ovarian cancer incidence and mortality also vary internationally, with incidence and mortality rates being higher in more developed regions than in less developed regions (Ferlay et al., 2015).

Aside from genetics (e.g., the higher proportion of mutations in cancer-predisposition genes among Ashkenazi Jewish women), the reasons behind the racial and ethnic differences in outcomes are unknown, but they might be explained in part by other variables such as differences in access to health care or the quality of that care (Baicker et al., 2005; IOM, 2003, 2012). Similarly, the reasons behind geographic variation in the demographics of ovarian cancer are unknown, and might be explained by other variables such as race and ethnicity (e.g., the higher proportion of Asian and Pacific Islanders in Hawaii) or differences in access to health care or the quality of that care in different geographic regions (Baicker et al., 2005; IOM, 2003, 2012). (See Chapter 4 for more on access and standards of care for women with ovarian cancer.) Overall, as noted previously, reporting on the demographics and epidemiology of ovarian cancer is challenging because of the fact that most of the data sources aggregate the various subtypes, and even when the data are reported by subtype, differences in the grading, classification, and nomenclature of the subtypes create challenges in summarizing and comparing data.

THE LANDSCAPE OF STAKEHOLDERS IN OVARIAN CANCER RESEARCH

Many public and private organizations are involved in funding, supporting, and carrying out ovarian cancer research, and they are involved in a variety of ways. The research is sometimes focused on ovarian cancers exclusively, but it sometimes looks at broader populations (e.g., women with gynecologic cancers). A complete cataloguing of every stakeholder in ovarian cancer research and of their individual efforts is beyond the scope of this report. Instead, this section offers an overview of the wide range of stakeholders and highlights the areas of ovarian cancer research that are getting the most attention and the methods used by stakeholders to communicate about new findings in ovarian cancer research.

Federal Stakeholders

While there are a number of different federal stakeholders in ovarian cancer research, the CDC, the U.S. Department of Defense (DoD), and the NIH (and the NCI in particular) are collectively responsible for the majority of the funding for ovarian cancer research at the federal level. The sections below give an overview of the funding levels and focus areas for these agencies. Where possible, the areas of focus are presented in alignment with the Common Scientific Outline (CSO), an international classification system used by cancer researchers to compare research portfolios. The CSO consists of seven broad areas of interest:

• Etiology (causes of cancer);
• Prevention;
• Early detection, diagnosis, and prognosis;
• Cancer control, survivorship, and outcomes research; and
• Scientific model systems (DoD, 2015b).

Centers for Disease Control and Prevention

The CDC conducts and supports studies, often in collaboration with partners, to “develop, implement, evaluate, and promote effective cancer prevention and control practices” (CDC, 2015). In general, the CDC approaches cancer by monitoring cancer demographics (surveillance), by conducting research and evaluation, by partnering with other stakeholders to help translate evidence, and by developing educational materials (CDC, 2015). Most of the CDC’s work in ovarian cancer is performed through its Division of Cancer Prevention and Control. 6 Since fiscal year (FY) 2000, the CDC has received about $5 million annually in congressional appropriations to support its Ovarian Cancer Control Initiative. In addition, in 2008 the CDC started receiving funds under Johanna’s Law to improve communication with women regarding gynecologic cancers. The CDC’s Inside Knowledge 7 campaign works to raise awareness about cervical, ovarian, uterine, vaginal, and vulvar cancers. Between 2010 and 2014, ads produced for the Inside Knowledge campaign were seen or heard around 3.5 million times and were worth a total of $136 million in donated ad value (CDC, 2014).

6 For more information, see http://www.cdc.gov/cancer/dcpc/about (accessed July 21, 2015).

7 For more information, see http://www.cdc.gov/cancer/knowledge (accessed September 1, 2015).

U.S. Department of Defense

The DoD’s Ovarian Cancer Research Program (OCRP) 8 received congressional appropriations from FY 1997 to FY 2014 totaling $236.45 million and received another $20 million in appropriations for FY 2015 (DoD, 2015a). Since the inception of the DoD OCRP, more than 130 ovarian cancer survivors have taken part in efforts to establish the OCRP’s priorities and research award mechanisms, and they have helped choose the research to be funded. From FY 1997 through FY 2013, the OCRP funded 313 awards in a variety of areas (see Figure 1-13 ). These awards show a focus on biology, treatment, and early detection, diagnosis, and prognosis. OCRP’s research priorities include understanding the precursor lesions, microenvironment, and pathogenesis of all types of ovarian cancer; developing and improving the performance and reliability of screening, diagnostic approaches, and treatment; developing or validating models to study initiation and progression; investigating tumor response to therapy; and enhancing the pool of ovarian cancer scientists (DoD, 2015a).

National Institutes of Health

The NCI of the NIH has initiated several activities to advance ovarian cancer research with intramural and extramural funding. In the past, five ovarian cancer–specific specialized programs of research excellence (SPOREs) in the United States conducted ovarian cancer research in early detection, imaging technologies, risk assessment, immunosuppression, and novel therapeutic approaches (NCI, 2015e). The NCI currently lists four active SPOREs for ovarian cancer.

The NCI is involved in ovarian cancer research in a variety of other ways. For example, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) is trying to understand the molecular basis of cancer in order to help improve the diagnosis, treatment, and prevention of cancer (NCI, 2015b). To accomplish these goals, CPTAC is using the data collected by The Cancer Genome Atlas (TCGA) analysis of ovarian tumors. The NCI has also supported a follow-up of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to analyze the biological material and risk factor information in order to better understand the risks and identify early biomarkers, including biomarkers for ovarian cancers. (See Chapter 3 for more on the PLCO Cancer Screening Trial.)

8 For more information, see http://cdmrp.army.mil/ocrp (accessed July 21, 2015).

FIGURE 1-13 Areas of ovarian cancer research funded by OCRP, FY 1997–2011. SOURCE: DoD, 2015b.

Overall, the NCI supported $100.6 million in research 9 related to ovarian cancer in FY 2013 while providing $559.2 million for breast cancer research, $63.4 million for cervical cancer research, and $17.8 million for endometrial cancer research (NCI, 2015g). However, the research projects listed as being related to ovarian cancer are not necessarily limited to ovarian cancer, and they include studies of multiple cancers (including ovarian cancer) or areas of cross-cutting research related to ovarian cancer. Fur-

9 The NCI notes that “the estimated NCI investment is based on funding associated with a broad range of peer-reviewed scientific activities” (NCI, 2015g). The NCI research portfolio for ovarian cancer may be found at http://fundedresearch.cancer.gov/nciportfolio/search/get?site=Ovarian+Cancer&fy=PUB2013 (accessed December 2, 2015).

thermore, data collected by the DoD 10 through the International Cancer Research Partnership indicates that the funded amount is significantly less when considering only new grants awarded by the NCI each year. Only 52 projects involving ovarian cancer research totaling $33.4 million were started in 2010, 58 new projects totaling $20.4 million in 2011, and 52 new projects totaling $16.3 million in 2012 (ICRP, 2015). Figure 1-14 shows that, like the DoD, the NCI portfolio for ovarian cancer research focuses primarily on treatment, biology, and early detection, diagnosis, and prognosis.

The Office of Cancer Survivorship (OCS), 11 part of the Division of Cancer Control and Population Sciences at the NCI, “works to enhance the quality and length of survival of all persons diagnosed with cancer and to minimize or stabilize adverse effects experienced during cancer survivorship. The office supports research that both examines and addresses the long- and short-term physical, psychological, social, and economic effects of cancer and its treatment among pediatric and adult survivors of cancer and their families” (NCI, 2014).

Figure 1-15 shows the areas of cancer survivorship research expertise at the NCI. As of October 2015, the Division of Cancer Control and Population Sciences had two open funding opportunities for general cancer survivorship research: one focused on the efficacy and impact of care planning, and the other examined the effects of physical activity and weight control interventions on cancer prognosis and survival (NCI, 2015a). Neither of these grant opportunities specified a focus on ovarian cancer survivorship.

Private Stakeholders

A wide variety of private stakeholders are engaged in ovarian cancer research, including professional societies, advocacy organizations, women’s health groups, and disease-specific foundations. In some cases, the organization specifically focuses on ovarian cancer and ovarian cancer research. However, many others focus on cancer or women’s health broadly (e.g., the American Cancer Society and the American Congress of Obstetricians and Gynecologists). Overall, private funders of ovarian cancer research tend to focus funding on biology and treatment, with very little funding directed toward the etiology of ovarian cancer or survivorship issues.

Private stakeholders can support young researchers with grant funding; provide training and educational opportunities; encourage collabora-

10 Personal communication, Patricia Modrow, data assembled by the U.S. Department of Defense Ovarian Cancer Research Program, January 16, 2015.

11 For more information about the OCS, see http://cancercontrol.cancer.gov/ocs (accessed May 15, 2015).

FIGURE 1-14 Areas of ovarian cancer research funded by the NCI. SOURCE: NCI, 2013.

tive, transdisciplinary efforts; and engage consumers, survivors, and their families. Examples of previous and current efforts by individual private stakeholders include

• The Health, Empowerment, Research, and Awareness Women’s Cancer Foundation awarded the Sean Patrick Multidisciplinary Collaborative Grant for cross-disciplinary projects to allow scientists to come together and test ideas that may not be fundable by other agencies (HERA, 2015).
• The Marsha Rivkin Center for Ovarian Cancer Research awards Bridge Funding Awards to researchers who are close to fundable grant scores for the DoD or the NIH but require additional data to ensure a successful resubmission (Rivkin Center, 2015).
• The Ovarian Cancer Research Fund (OCRF) provides funding to researchers at all stages of their careers; OCRF awards include funding for recent graduates, newly independent researchers who are building laboratories, and senior researchers working on collaborative projects (OCRF, 2015).

FIGURE 1-15 Expertise areas for cancer survivorship research at the NCI. SOURCE: NCI, 2015c.

• The Society of Gynecologic Oncology (SGO) released Pathways to Progress in Women’s Cancer in 2011, a research agenda based on discussions of working groups at a 2010 research summit. One working group focused on ovarian cancers, and the report provides short-term, intermediate, and long-term research priorities (SGO, 2011).
• The Honorable Tina Brozman Foundation for Ovarian Cancer Research (also known as Tina’s Wish) funds research specifically in the early detection and prevention of ovarian cancer and also supports a consortium to advance such research (Tina’s Wish, 2015).

The Role of Advocacy in Ovarian Cancer Research

Advocacy has positively affected ovarian cancer research, public knowledge, and awareness. Many different types of people play the role of

advocate—women with ovarian cancer, partners, family members, health care professionals, and activists—and their advocacy efforts range from the individual, patient level to the societal level, but all of these different efforts have had effects on funding efforts, policy change, and the direction of research.

Patients self-advocate by taking active roles in their own care. Researchers have recognized this concept of self-advocacy as an important part of patient-centered care, and it has been described as “a distinct type of advocacy in which an individual or group supports and defends their interests either in the face of a threat or proactively to meet their needs” (Hagan and Donovan, 2013, p. 3). However, despite claims that self-advocacy may improve quality of life, health care use, and symptom management, these potential effects have not been adequately studied.

Nurses can serve as advocates for patients by protecting patients’ rights, incorporating patients’ beliefs and values into their care plans, and respecting the autonomy of the patient to ensure access to quality care (Temple, 2002). Advocacy groups provide education, information, and personal support to patients, family caregivers, and the general public. Many advocacy groups also use lobbying efforts to influence policy, including the direction of research and funding.

Large-scale advocacy efforts have arguably had a great impact on cancer research and funding. In the late 1990s, survivors advocated for wider recognition of early-stage ovarian cancer symptoms. Until that time, physicians and medical textbooks had claimed that women did not experience symptoms until advanced stages of disease (Twombly, 2007). Johanna’s Law is considered a victory of advocacy groups’ lobbying efforts. Furthermore, Congress has appropriated funds for ovarian cancer research and education programs since FY 1997. The establishment and unified efforts of national advocacy organizations are partially responsible for the significant funding increases in the intervening years (Temple, 2002).

Advocacy groups have also been integral to the advancement of ovarian cancer research through their participation in the design and administration of studies (Armstrong et al., 2014; Holman et al., 2014). The scientific literature emphasizes the importance of patient advocates in patient-centered research, citing examples of the collaboration between researchers and patient advocates in research studies (Armstrong et al., 2014; Holman et al., 2014; Staton et al., 2008).

Several large advocacy groups at the national and international levels focus on ovarian cancer. For example, the Ovarian Cancer National Alliance (OCNA), a national advocacy organization, has among its activities the Survivors Teaching Students: Saving Women’s Lives® program, which is aimed at educating caregivers and medical, nursing, and other professional

students about the early signs and symptoms of ovarian cancer. Recently, OCNA spearheaded the formation of the first congressional Ovarian Cancer Caucus with the support of Rosa DeLauro (D-CT) and Sean Duffy (R-WI). The first meeting was held on September 29, 2015, in Washington, DC. The National Ovarian Cancer Coalition (NOCC), another national advocacy organization, funds the Teal Initiative to improve education and awareness. NOCC also supports specific research in ovarian cancer and provides survivor support, primarily through its Faces of Hope program, which is “dedicated to improving the quality of life for women affected by ovarian cancer, as well as providing support for their loved ones and caregivers” (NOCC, 2014). At the international level, the charity Ovarian Cancer Action encourages collaboration among ovarian cancer researchers around the world. Half of its funds go to the Ovarian Cancer Action Research Centre in the United Kingdom, which exclusively supports “research that can be translated into meaningful outcomes for real women in real life” (Ovarian Cancer Action, 2015). In addition, every few years Ovarian Cancer Action hosts an international forum to bring researchers together to share information, inspire collaboration, and develop white papers. In 2011 the forum developed the paper Rethinking Ovarian Cancer: Recommendations for Improving Outcomes, which outlined recommendations for improving outcomes for women with ovarian cancer (Vaughan et al., 2011). A number of other advocacy groups work at the local and national levels to support research in ovarian cancer.

The Role of Consortia and Collaboration in Ovarian Cancer Research

Because of the relative rarity of ovarian cancers, especially when subdivided according to subtypes, collaborative research efforts are necessary in order to collect sufficient data for statistically significant results. Many consortia and multisite studies have evolved to promote the sharing of biospecimens, clinical data, and epidemiologic data in order to ensure sufficient sample sizes in studies. These consortia and collaborations operate at both the national and international levels. Common uses of consortia include carrying out research on the genetic and nongenetic risk factors of developing ovarian cancers, studying mechanisms of disease relapse and resistance, and identifying newer therapies (AOCS, 2015; COGS, 2009; NRG Oncology, 2015; OCAC, 2015; OCTIPS, 2015). Furthermore, groups will often team together in coalitions to promote transdisciplinary research and also to promote the translation and dissemination of information. For example, in 2015, OCNA, NOCC, and OCRF provided funding for the Stand Up To Cancer (SU2C) Dream Team for ovarian cancer. This team will bring together experts in DNA repair, translational investigators, and

clinicians “to create new programs in discovery, translation, and clinical application, while cross-fertilizing and educating researchers at all levels to enhance collaboration and catalyze translational science” (SU2C, 2015).

Consortia and coalitions have had clear, measureable impacts on the research base for ovarian cancers. For example, as a result of the Collaborative Oncological Gene-environment Study (COGS), 14 new markers for risk of ovarian cancer were identified (only 8 had been known before COGS) (COGS, 2014). Based on the work of this coalition, TCGA researchers completed a detailed analysis of ovarian cancer, which confirmed that mutations in the TP53 gene (which encodes a protein that normally suppresses tumor development) are present in nearly all HGSCs (Bell et al., 2011). The analysis also examined gene expression patterns and identified signatures that correlate with survival outcomes, affirmed four subtypes of HGSCs, and identified dozens of genes that might be targeted by gene therapy (NIH, 2011, 2015b).

NCI’s National Clinical Trials Network

In 1955 the NCI established the Clinical Trials Cooperative Group Program. As the science of cancer treatment was evolving, researchers realized that collaborative efforts were necessary to accrue sufficient numbers for clinical trials in order to more rapidly compare the value of new therapies to existing standards of care, particularly for the use of chemotherapy in the treatment of solid tumors (DiSaia et al., 2006; IOM, 2010b). The work of the cooperative groups led to advances in the treatment of women with ovarian cancer specifically, including a demonstration of the value of adding paclitaxel to cisplatin, confirmation of the value of cytoreductive surgery, and a demonstration of the value of carboplatin for late-stage ovarian cancers (IOM, 2010b). The groups have also studied issues related to the quality of life and the prevention of ovarian cancer. Between 1970 and 2005, clinical trials of the Gynecologic Oncology Group (GOG) alone included approximately 35,000 women with ovarian cancer (DiSaia et al., 2006).

In 2014, based in part on the IOM report A National Cancer Clinical Trials System for the 21st Century , the NCI transformed the cooperative group program into the new National Clinical Trials Network (IOM, 2010b, 2011, 2013b; NCI, 2015f). This reorganization consolidated nine cooperative groups into five new groups:

• The Alliance for Clinical Trials in Oncology;
• The ECOG-ACRIN Cancer Research Group (a merger of two cooperative groups: the Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network);
• NRG Oncology (a merger of three cooperative groups: the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the GOG);
• The Southwest Oncology Group; and
• The Children’s Oncology Group (NCI, 2015f).

PREVIOUS WORK AT THE INSTITUTE OF MEDICINE

The IOM has a long history of producing reports related to various aspects of cancer care, and many of them are directly relevant to this current study. This section describes some examples of previous IOM work that is related to the work of this committee.

Prevention and Early Detection

In 2005 the IOM report Saving Women’s Lives: Strategies for Improving Breast Cancer Detection and Diagnosis (IOM, 2005) recommended the development of tools to identify the women who would benefit most from breast cancer screening based on “individually tailored risk prediction techniques that integrate biologic and other risk factors.” The report also called for the development of tools that “facilitate communication regarding breast cancer risk to the public and to health care providers.” In addition, the report called for more research on breast cancer screening and detection technologies, including research on various aspects of technology adoption (e.g., monitoring the use of technology in clinical practice).

A 2007 IOM report, Cancer Biomarkers , offered recommendations on the methods, tools, and resources needed to discover and develop biomarkers for cancer; guidelines, standards, oversight, and incentives needed for biomarker development; and the methods and processes needed for clinical evaluation and adoption of such biomarkers (IOM, 2007a). Specific recommendations from the report included establishing international consortia to generate and share data, supporting high-quality biorepositories of prospectively collected samples, and developing criteria for conditional coverage of new biomarker tests. Subsequently, in 2010, an IOM report, Evaluation of Biomarkers and Surrogate Endpoints in Chronic Disease , outlined a framework for the evaluation of biomarkers (IOM, 2010a).

In Initial National Priorities for Comparative Effectiveness Research (IOM, 2009), the committee offered two priorities that are relevant to ovarian cancer genetics: “Compare the effectiveness of adding informa-

tion about new biomarkers (including genetic information) with standard care in motivating behavior change and improving clinical outcomes” and “Compare the effectiveness of genetic and biomarker testing and usual care in preventing and treating breast, colorectal, prostate, lung, and ovarian cancer, and possibly other clinical conditions for which promising biomarkers exist” (IOM, 2009, p. 4).

In 2007, the IOM’s National Cancer Policy Forum hosted a workshop on cancer-related genetic testing and counseling. According to the published summary of that workshop, participants observed that “genetic testing and counseling are becoming more complex and important for informing patients and families of risks and benefits of certain courses of action, and yet organized expert programs are in short supply. The subject matter involves not only the scientific and clinical aspects but also workforce and reimbursement issues, among others” (IOM, 2007b)

Clinical Trials

The 2005 IOM report on breast cancer detection called for public health campaigns and for improved information and communication about the value of participation in clinical trials (including the participation of healthy individuals).

A 2010 report, A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program (IOM, 2010b), called for the restructuring of the NCI Cooperative Group Program and set four goals:

• Improve the speed and efficiency of the design, launch, and conduct of clinical trials (e.g., improve collaboration among stakeholders);
• Incorporate innovative science and trial design into cancer clinical trials (e.g., support standardized central biorepositories, develop and evaluate novel trial designs);
• Improve the means of prioritization, selection, support, and completion of cancer clinical trials (e.g., develop national unified standards); and
• Incentivize the participation of patients and physicians in clinical trials (e.g., develop electronic tools to alert clinicians to available trials for specific patients, encourage eligibility criteria to allow broad participation, cover cost of patient care in trials).

Palliative and End-of-Life Care

Improving Palliative Care for Cancer (IOM, 2001) called for incorporating palliative care into clinical trials. The report also noted that infor-

mation on palliative and end-of-life care is largely absent from materials developed for the public about cancer treatment, and the committee recommended strategies for disseminating information and improving education about end-of-life care. The report recommended that the NCI require comprehensive cancer centers to carry out research in palliative care and symptom control and that the Health Care Finance Administration (now the Centers for Medicare & Medicaid Services) fund demonstration projects for service delivery and reimbursement that integrate palliative care throughout the course of the disease.

Dying in America (IOM, 2015) noted that palliative care can begin early in the course of treatment, in conjunction with treatment, and can continue throughout the continuum of care. The report further observed that “a palliative approach can offer patients near the end of life and their families the best chance of maintaining the highest possible quality of life for the longest possible time” (IOM, 2015, p. 1).

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis (IOM, 2013a) addressed the delivery of cancer care, including palliative and end-of-life care. The study called for providing patients and their families with understandable information about palliative (and other) care and recommended that “the cancer care team should provide patients with end-of-life care consistent with their needs, values, and preferences” (IOM, 2013a, p. 9).

Communication and Survivorship

From Cancer Patient to Cancer Survivor (IOM, 2006) called for actions to raise awareness about the needs of cancer survivors, including the establishment of cancer survivorship as a distinct phase of cancer care. In 2008, the IOM report Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs (IOM, 2008) recommended that facilitating effective communication between patients and care providers, identifying psychosocial health needs, and engaging and supporting patients in managing their illnesses should all be considered as part of the standard of care. The report emphasized the importance of educating patients and their families and of enabling patients to actively participate in their own care by providing tools and training in how to obtain information, make decisions, solve problems, and communicate more effectively with their health care providers. The report further called for the government to invest in a large-scale demonstration and evaluation of various approaches to the efficient provision of psychosocial health care.

Women’s Health Research (IOM, 2010c) found that there are many barriers to the translation of research findings in general and that some have aspects that are “peculiar to women.” The committee recommended

specific research on how to translate research findings on women’s health into clinical practice and public health policies.

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis (IOM, 2013a) called for providing patients and their families with “understandable information on cancer prognosis, treatment benefits and harms, palliative care, psychosocial support, and estimates of the total and out-of-pocket costs of cancer care.” The report further called for the development of decision aids to be made available through print, electronic, and social media; for the formal training of cancer care team members in communication; for the communication of relevant and personalized information at key decision points along the continuum of cancer care; and for consideration of patients’ individual needs, values, and preferences when developing a care plan, including end-of-life care. The report also called for the identification and public dissemination of evidence-based information about cancer care practices that are unnecessary or for which the harm may outweigh the benefits.

OVERVIEW OF THE REPORT

This chapter has provided an overview of the study charge and the committee’s approach to its work. It has also provided an introduction to the challenges in ovarian cancer research, to defining and classifying ovarian cancers, to the patterns and demographics of the disease, and to the landscape of stakeholders in ovarian cancer research. The remaining chapters follow the research framework outlined in Figure 1-1 .

Chapter 2 describes the current state of the science in the biology of ovarian cancers, thus providing a foundation for the descriptions of most of the other ovarian cancer research covered in this report. This background includes information about the characteristics of specific ovarian carcinomas, the role of the tumor microenvironment, and experimental model systems.

Chapter 3 builds on this to discuss research on the prevention and early detection of ovarian cancers. On the topic of risk assessment, the chapter includes discussions of a wide range of genetic and nongenetic risk factors for the development of an ovarian cancer, risk-prediction models, and genetic testing. Concerning prevention, both surgical and nonsurgical prevention strategies are discussed. And on the topic of early detection, the chapter has descriptions of various approaches to identifying ovarian cancers earlier, including biomarkers and imaging techniques, and a discussion of the challenges in performing screening in both general and high-risk populations.

Chapter 4 describes the research base for the diagnosis and treatment of women newly diagnosed with ovarian cancer as well as for women with

relapsed ovarian cancer. The chapter outlines research on current standards of care and also explores the development of novel therapeutics such as anti-angiogenics, poly ADP ribose polymerase (PARP) inhibitors, and immunotherapy. Later, the chapter discusses issues of clinical trial development and use as they relate specifically to research in ovarian cancer.

Chapter 5 discusses research on survivorship and management issues along the entire care continuum from diagnosis to end of life. Furthermore, women who are at a high risk for developing cancer (sometimes referred to as “previvors”) may have psychosocial needs of their own that should be studied. Overall, research that focuses specifically on survivorship and management issues in ovarian cancer is scarce; it may thus be necessary to apply research from broader studies of survivorship to women with ovarian cancer. The chapter discusses the research base for the unique issues of survivorship and management for women with ovarian cancer and their families, including managing the physical side effects of treatment, addressing unique psychosocial impacts, engaging women in their own self-care, and addressing end-of-life concerns.

Chapter 6 summarizes the findings and conclusions of the previous chapters in order to provide a cohesive set of recommendations for prioritizing research on ovarian cancers in such a way as to have the greatest impact on reducing morbidity and mortality from the disease.

Chapter 7 gives an overview of research on the translation and dissemination of new information to the general public, providers, researchers, policy makers, and others. The chapter reflects on the messages within the previous chapters that are ready to be communicated and identifies potential avenues for communicating these messages.

Finally, the report contains five appendixes. Appendix A contains a list of key acronyms used throughout the report. Appendix B contains a glossary of key terms. Appendix C includes a listing of currently active studies on epithelial ovarian cancer (based on information available through www.ClinicalTrials.gov ) in order to give a sense of where emphasis is being placed in future research. Appendix D lists the agendas of the committee’s workshops. Appendix E contains the biographical sketches of the committee members and project staff.

ACS (American Cancer Society). 2015. Cancer facts & figures 2015. Atlanta, GA: American Cancer Society.

AOCS (Australian Ovarian Cancer Study). 2015. AOCS programme. http://www.aocstudy.org/hp_programme.asp (accessed July 21, 2015).

Armstrong, J., M. Toscano, N. Kotchko, S. Friedman, M. D. Schwartz, K. S. Virgo, K. Lynch, J. E. Andrews, C. X. Aguado Loi, J. E. Bauer, C. Casares, R. T. Teten, M. R. Kondoff, A. D. Molina, M. Abdollahian, L. Brand, G. S. Walker, and R. Sutphen. 2014. American BRCA outcomes and utilization of testing (ABOUT) study: A pragmatic research model that incorporates personalized medicine/patient-centered outcomes in a real world setting. Journal of Genetic Counseling 24(1):18-28.

Baicker, K., A. Chandra, and J. Skinner. 2005. Geographic variation in health care and the problem of measuring racial disparities. Perspectives in Biology and Medicine 48(Suppl 1): S42-S53.

Bell, D., A. Berchuck, M. Birrer, J. Chien, D. W. Cramer, et al. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474(7353):609-615.

Berek, J. S., and Bast, R. C., Jr. 2003. Epithelial Ovarian Cancer. In: Holland-Frei Cancer Medicine , 6th ed., edited by D. W. Kufe, R. E. Pollock, R. R. Weichselbaum, et al. Hamilton, Ontario: B.C. Decker.

Braicu, E. I., J. Sehouli, R. Richter, K. Pietzner, C. Denkert, and C. Fotopoulou. 2011. Role of histological type on surgical outcome and survival following radical primary tumour debulking of epithelial ovarian, fallopian tube and peritoneal cancers. British Journal of Cancer 105(12):1818-1824.

CDC (Centers for Disease Control and Prevention). 2014. 2014 campaign highlights. http://www.cdc.gov/cancer/knowledge/pdf/cdc_ik_2014_year_end_report.pdf (accessed October 20, 2015).

CDC. 2015. Chronic disease prevention and health promotion: Addressing the cancer burden at a glance. http://www.cdc.gov/chronicdisease/resources/publications/aag/dcpc.htm (accessed October 5, 2015).

COGS (Collaborative Oncological Gene-environment Study). 2009. Concept and project objectives. http://www.cogseu.org/index.php/concept-and-project-objectives (accessed July 23, 2015).

COGS. 2014. Executive summary. http://www.cogseu.org (accessed July 23, 2015).

DiSaia, P., D. Alberts, W. Beck, M. Birrer, J. Blessing, et.al. 2006. Gynecologic Oncology Group: Report of 35 years of excellence in clinical research. Philadelphia, PA: Gynecologic Oncology Group.

Dizon, D. S., T. Tejada-Berges, S. Koelliker, M. Steinhoff, and C. O. Granai. 2006. Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient. Gynecologic and Obstetric Investigation 62(4):226-228.

DoD (U.S. Department of Defense). 2015a. Ovarian cancer. http://cdmrp.army.mil/ocrp (accessed September 21, 2015).

DoD. 2015b. Program portfolios by CSO categories. http://cdmrp.army.mil/pubs/portfolio/prgPortfolio.shtml (accessed September 21, 2015).

Ferlay, J., I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray. 2015. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer 136(5):E359-E386.

Gajjar, K., G. Ogden, M. I. Mujahid, and K. Razvi. 2012. Symptoms and risk factors of ovarian cancer: A survey in primary care. ISRN Obstetrics and Gynecology 2012:754197.

Gilks, C. B., D. N. Ionescu, S. E. Kalloger, M. Kobel, J. Irving, B. Clarke, J. Santos, N. Le, V. Moravan, K. Swenerton, and Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency. 2008. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Human Pathology 39(8):1239-1251.

Goff, B. 2012. Symptoms associated with ovarian cancer. Clinical Obstetrics and Gynecology 55(1):36-42.

Goff, B. A., L. Mandel, H. G. Muntz, and C. H. Melancon. 2000. Ovarian carcinoma diagnosis: Results of a national ovarian cancer survey. Cancer 89(10):2068-2075.

Goff, B. A., L. S. Mandel, C. H. Melancon, and H. G. Muntz. 2004. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. Journal of the American Medical Association 291(22):2705-2712.

Gurung, A., T. Hung, J. Morin, and C. B. Gilks. 2013. Molecular abnormalities in ovarian carcinoma: Clinical, morphological and therapeutic correlates. Histopathology 62(1):59-70.

Gynecologic Oncology Group (GOG). 2015. GOG Industry Collaboration Team. http://www.gog.org/AdminSite/public/ict/ict.html (accessed December 14, 2015).

Hagan, T. L., and H. S. Donovan. 2013. Ovarian cancer survivors’ experiences of self-advocacy: A focus group study. Oncology Nursing Forum 40(2):140-147.

Hage, J. J., M. L. Dekker, R. B. Karim, R. H. M. Verheijen, and E. Bloemena. 2000. Ovarian cancer in female-to-male transsexuals: Report of two cases. Gynecologic Oncology 76(3):413-415.

HERA. 2015. Sean Patrick multidisciplinary collaborative grant. http://www.herafoundation.org/grants-research/science-grants/sp-grant (accessed September 21, 2015).

Holman, L. L., S. Friedman, M. S. Daniels, C. C. Sun, and K. H. Lu. 2014. Acceptability of prophylactic salpingectomy with delayed oophorectomy as risk-reducing surgery among BRCA mutation carriers. Gynecologic Oncology 133(2):283-286.

Howlader, N., A. M. Noone, M. Krapcho, J. Garshell, D. Miller, S. F. Altekruse, C. L. Kosary, M. Yu, J. Ruhl, Z. Tatalovich, A. Mariotto, D. R. Lewis, H. S. Chen, E. J. Feuer, and K. A. Cronin. 2015. SEER cancer statistics review, 1975–2012. Bethesda, MD: National Cancer Institute.

ICRP (International Cancer Research Partnership). 2015. Search the ICRP database. https://www.icrpartnership.org/database.cfm (accessed October 20, 2015).

IOM (Institute of Medicine). 2001. Improving palliative care for cancer. Washington, DC: National Academy Press.

IOM. 2003. Unequal treatment: Confronting racial and ethnic disparities in health care. Washington, DC: The National Academies Press.

IOM. 2005. Saving women’s lives: Strategies for improving breast cancer detection and diagnosis: A Breast Cancer Research Foundation and Institute of Medicine symposium. Washington, DC: The National Academies Press.

IOM. 2006. From cancer patient to cancer survivor: Lost in transition. Washington, DC: The National Academies Press.

IOM. 2007a. Cancer biomarkers: The promises and challenges of improving detection and treatment. Washington, DC: The National Academies Press.

IOM. 2007b. Cancer-related genetic testing and counseling: Workshop proceedings. Washington, DC: The National Academies Press.

IOM. 2008. Cancer care for the whole patient: Meeting psychosocial health needs. Washington, DC: The National Academies Press.

IOM. 2009. Initial national priorities for comparative effectiveness research. Washington, DC: The National Academies Press.

IOM. 2010a. Evaluation of biomarkers and surrogate endpoints in chronic disease. Washington, DC: The National Academies Press.

IOM. 2010b. A national cancer clinical trials system for the 21st century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: The National Academies Press.

IOM. 2010c. Women’s health research: Progress, pitfalls, and promise. Washington, DC: The National Academies Press.

IOM. 2011. Implementing a national cancer clinical trials system for the 21st century: Workshop summary. Washington, DC: The National Academies Press.

IOM. 2012. Geographic adjustment in Medicare payment: Phase II: Implications for access, quality, and efficiency. Washington, DC: The National Academies Press.

IOM. 2013a. Delivering high-quality cancer care: Charting a new course for a system in crisis. Washington, DC: The National Academies Press.

IOM. 2013b. Implementing a national cancer clinical trials system for the 21st century: Second workshop summary. Washington, DC: The National Academies Press.

IOM. 2015. Dying in America: Improving quality and honoring individual preferences near the end of life. Washington, DC: The National Academies Press.

Jones, S. C., C. A. Magee, J. Francis, K. Luxford, P. Gregory, H. Zorbas, and D. C. Iverson. 2010. Australian women’s awareness of ovarian cancer symptoms, risk and protective factors, and estimates of own risk. Cancer Causes and Control 21(12):2231-2239.

Kalloger, S. E., M. Köbel, S. Leung, E. Mehl, D. Gao, K. M. Marcon, C. Chow, B. A. Clarke, D. G. Huntsman, and C. B. Gilks. 2011. Calculator for ovarian carcinoma subtype prediction. Modern Pathology 24(4):512-521.

Lockwood-Rayermann, S., H. S. Donovan, D. Rambo, and C. W. Kuo. 2009. Women’s awareness of ovarian cancer risks and symptoms. American Journal of Nursing 109(9):36-45; quiz 46.

Mackay, H. J., M. F. Brady, A. M. Oza, A. Reuss, E. Pujade-Lauraine, A. M. Swart, N. Siddiqui, N. Colombo, M. A. Bookman, J. Pfisterer, and A. du Bois on behalf of the Gynecologic Cancer InterGroup. 2010. Prognostic relevance of uncommon ovarian histology in women with Stage III/IV epithelial ovarian cancer. International Journal of Gynecological Cancer 20(6):945-952.

Malpica, A., M. T. Deavers, K. Lu, D. C. Bodurka, E. N. Atkinson, D. M. Gershenson, and E. G. Silva. 2004. Grading ovarian serous carcinoma using a two-tier system. American Journal of Surgical Pathology 28(4):496-504.

Moslehi, R., W. Chu, B. Karlan, D. Fishman, H. Risch, A. Fields, D. Smotkin, Y. Ben-David, J. Rosenblatt, D. Russo, P. Schwartz, N. Tung, E. Warner, B. Rosen, J. Friedman, J. S. Brunet, and S. A. Narod. 2000. BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. American Journal of Human Genetics 66(4):1259-1272.

Munnell, E. W. 1952. Ovarian carcinoma: Predisposing factors, diagnosis, and management. Cancer 5(6):1128-1133.

NCI (National Cancer Institute). 2013. A snapshot of ovarian cancer. http://www.cancer.gov/research/progress/snapshots/ovarian (accessed October 1, 2015).

NCI. 2014. Office of cancer survivorship: Mission. http://cancercontrol.cancer.gov/ocs/about/mission.html (accessed September 21, 2015).

NCI. 2015a. Apply for cancer control grants. http://cancercontrol.cancer.gov/funding_apply.html#ocs (accessed September 21, 2015).

NCI. 2015b. Clinical proteomic tumor analysis consortium. http://proteomics.cancer.gov/programs/cptacnetwork (accessed October 19, 2015).

NCI. 2015c. Expertise in cancer survivorship research. http://cancercontrol.cancer.gov/ocs/about/staff.html (accessed September 21, 2015).

NCI. 2015d. NCI dictionary of cancer terms. http://www.cancer.gov/publications/dictionaries/cancer-terms (accessed September 16, 2015).

NCI. 2015e. Ovarian SPORES. http://trp.cancer.gov/spores/ovarian.htm (accessed October 7, 2015).

NCI. 2015f. An overview of NCI’s National Clinical Trials Network. http://www.cancer.gov/research/areas/clinical-trials/nctn (accessed December 14, 2015).

NCI. 2015g. A snapshot of ovarian cancer http://www.cancer.gov/research/progress/snapshots/ovarian (accessed December 2, 2015).

NIH (National Institutes of Health). 2011. News release: The Cancer Genome Atlas completes detailed ovarian cancer analysis. http://cancergenome.nih.gov/newsevents/newsannouncements/ovarianpaper (accessed July 21, 2015).

NIH. 2015a. Frequently asked questions. https://rarediseases.info.nih.gov/about-gard/pages/31/frequently-asked-questions (accessed October 7, 2015).

NIH. 2015b. Ovarian serous cystadenocarcinoma. http://cancergenome.nih.gov/cancers-selected/ovarian (accessed July 21, 2015).

NOCC (National Ovarian Cancer Coalition). 2014. Empowering the community: Ovarian cancer is more than a woman’s disease. http://ovarian.org/docs/NOCC_2013-14_Impact_Report.pdf (accessed October 20, 2015).

NRG Oncology. 2015. Scientific focus. https://www.nrgoncology.org/About-Us/Scientific-Focus (accessed July 22, 2015).

OCAC (Ovarian Cancer Association Consortium). 2015. About OCAC. http://apps.ccge.medschl.cam.ac.uk/consortia/ocac//aims/aims.html (accessed July 23, 2015).

OCRF (Ovarian Cancer Research Fund). 2015. What we fund. http://www.ocrf.org/ovarian-cancer-research/what-we-fund (accessed September 21, 2015).

OCTIPS (Ovarian Cancer Therapy—Innovative Models Prolong Survival). 2015. Research topics. http://www.octips.eu/research-topics (accessed July 21, 2015).

Ovarian Cancer Action. 2015. Who are Ovarian Cancer Action? http://ovarian.org.uk/about-us/our-mission-statement (accessed July 21, 2015).

Pennington, K. P., T. Walsh, M. I. Harrell, M. K. Lee, C. C. Pennil, et al. 2014. Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas. Clinical Cancer Research 20(3):764-775.

Prat, J. 2012. New insights into ovarian cancer pathology. Annals of Oncology 23(Suppl 10):x111-x117.

Rauh-Hain, J. A., E. J. Diver, J. T. Clemmer, L. S. Bradford, R. M. Clark, W. B. Growdon, A. K. Goodman, D. M. Boruta, 2nd, J. O. Schorge, and M. G. del Carmen. 2013. Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis. Gynecologic Oncology 131(1):46-51.

Ries, L. A. G., J. L. Young, G. E. Keel, M. P. Eisner, Y. D. Lin, and M. J. Horner. 2007. Cancer survival among adults: U.S. SEER program, 1988–2001, patient and tumor characteristics. Bethesda, MD: National Cancer Institute.

Rivkin Center. 2015. Bridge funding award. http://www.marsharivkin.org/research/bridge_funding_award.html (accessed September 21, 2015).

Scully, R. E., R. H. Young, and P. B. Clement. 1999. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament. In Atlas of Tumor Pathology (Third Series, Fascicle 23) . Washington, DC: American Registry of Pathology.

SEER (Surveillance, Epidemiology, and End Results) Program. 2015. Fast stats: An interactive tool for access to SEER cancer statistics. http://www.seer.cancer.gov/faststats/index.php (accessed December 3, 2015).

Seidman, J. D., R. J. Kurman, and B. M. Ronnett. 2003. Primary and metastatic mucinous adenocarcinomas in the ovaries: Incidence in routine practice with a new approach to improve intraoperative diagnosis. American Journal of Surgical Pathology 27(7):985-993.

Seidman, J. D., I. Horkayne-Szakaly, M. Haiba, C. R. Boice, R. J. Kurman, and B. M. Ronnett. 2004. The histologic type and stage distribution of ovarian carcinomas of surface epithelial origin. International Journal of Gynecological Pathology 23(1):41-44.

SGO (Society of Gynecologic Oncology). 2011. Pathways to progress in women’s cancer: A research agenda proposed by the Society of Gynecologic Oncology. https://www.sgo.org/wp-content/uploads/2012/10/Pathways-to-Progress.pdf (accessed September 21, 2015).

Shih, I.-M., and R. J. Kurman. 2004. Ovarian tumorigenesis. The American Journal of Pathology 164(5):1511-1518.

Silverberg, S. G. 2000. Histopathologic grading of ovarian carcinoma: A review and proposal. International Journal of Gynecological Pathology 19(1):7-15.

Singh, S. D., A. B. Ryerson, M. Wu, and J. S. Kaur. 2014. Ovarian and uterine cancer incidence and mortality in American Indian and Alaska Native women, United States, 1999–2009. American Journal of Public Health 104(Suppl 3):S423-S431.

Staton, A. D., A. W. Kurian, K. Cobb, M. A. Mills, and J. M. Ford. 2008. Cancer risk reduction and reproductive concerns in female BRCA1/2 mutation carriers. Familial Cancer 7(2):179-186.

SU2C (Stand Up To Cancer). 2015. SU2C-ovarian cancer research fund-ovarian cancer national alliance-national ovarian cancer coalition dream team: DNA repair therapies for ovarian cancer. https://www.standup2cancer.org/dream_teams/view/su2c_ocrf_ocna_nocc_ovarian_cancer_dream_team (accessed September 21, 2015).

Temple, S. V. 2002. The advocacy movement in gynecologic oncology. Seminars in Oncology Nursing 18(3):231-235.

Tina’s Wish. 2015. About Tina’s Wish. http://www.tinabrozmanfoundation.org/about-tinas-wish (accessed October 22, 2015).

Twombly, R. 2007. Cancer killer may be “silent” no more. Journal of the National Cancer Institute 99(18):1359-1361.

Vaughan, S., J. I. Coward, R. C. Bast, Jr., A. Berchuck, J. S. Berek, et al. 2011. Rethinking ovarian cancer: Recommendations for improving outcomes. Nature Reviews: Cancer 11(10):719-725.

In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease—several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors.

Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

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Ovarian cancer: New treatments and research

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By Nicole Brudos Ferrara

Three cancers — ovarian epithelial cancer, fallopian tube cancer and primary peritoneal cancer — are commonly called ovarian cancer. They arise from the same kind of tissue and are treated similarly.

"The ovaries and fallopian tubes are so anatomically close to each other that we sometimes can't tell if the cancer is coming from the ovary or the fallopian tube," says S. John Weroha, M.D., Ph.D. , a Mayo Clinic oncologist and chair of Mayo Clinic Comprehensive Cancer Center's Gynecologic Cancer Disease Group. "When we diagnose patients with primary peritoneal cancer, I explain that under the microscope, and in the pattern of spread through the body, it looks like ovarian cancer even though the ovaries are not involved."

Primary peritoneal cancer forms in the peritoneum, the tissue that lines the abdominal cavity and the organs within it. Fallopian tube cancer forms in the tissue lining the inside of the tubes that eggs travel through to move from the ovaries to the uterus.

About 85% to 90% of ovarian cancers are ovarian epithelial cancers, also known as epithelial ovarian carcinomas, which form in the tissue lining the outside of the ovaries.

Dr. Weroha says new treatments are helping more people survive ovarian cancer of all types, and researchers are studying new treatments and screening methods in clinical trials. If you've been diagnosed with ovarian cancer, he wants you to know there is hope. Here's why:

New targeted therapies are improving survival.

Surgery and chemotherapy are no longer the only options for ovarian cancer treatment . Targeted therapies use drugs to target and attack cancer cells. These include monoclonal antibodies and poly (ADP-ribose) polymerase, or PARP, inhibitors.

Monoclonal antibodies

Monoclonal antibodies are molecules engineered in the laboratory to find and attach to specific proteins associated with cancer cells. Bevacizumab is a monoclonal antibody used with chemotherapy to treat ovarian cancer recurrence by preventing the growth of new blood vessels that tumors need to grow.

Researchers are combining bevacizumab with new drugs to improve outcomes. One example is a monoclonal antibody recently approved by the Food and Drug Administration (FDA) called mirvetuximab soravtansine for people with ovarian cancer recurrence. This drug is used when a person's cancer was previously treated with at least one systemic therapy to target a protein called folate receptor alpha.

"Ovarian cancers have many folate receptors. Most normal cells don't," says Dr. Weroha. "This drug is an antibody that has chemotherapy stuck onto it. Think of it as a guided missile traveling the body and sticking to cells with folate receptors. In patients whose ovarian cancer has recurred and whose tumors have many folate receptors, mirvetuximab soravtansine can shrink tumors far better than any other therapy. The response rate is about double what you see with any other treatment."

PARP inhibitors

PARP inhibitors are drugs that block DNA repair, which may cause cancer cells to die. Olaparib is an example of a PARP inhibitor used to prevent recurrence in people with ovarian cancer whose tumors have BRCA1 or BRCA2 gene mutations. Research has shown that olaparib can significantly improve survival without recurrence in people with this diagnosis. "This is a front-line treatment, which means this is part of the first treatment regimen patients receive when they are newly diagnosed," says Dr. Weroha.

A vaccine may one day be used to fight ovarian cancer.

Matthew Block, M.D., Ph.D. , a Mayo Clinic medical oncologist, and Keith Knutson, Ph.D. , a Mayo Clinic researcher, are developing a vaccine to prevent ovarian cancer tumors from returning in people with advanced ovarian cancer whose tumors have recurred after surgery and chemotherapy.

White blood cells are extracted from a blood draw and manufactured to become dendritic cells — immune cells that boost immune responses. These cells are returned to the patient in vaccine form to trigger the immune system to recognize and fight the cancer.

The vaccine will be given in combination with an immunotherapy drug called pembrolizumab to identify and kill any tumors that don't respond to the dendritic cells.

"Pembrolizumab is in a category of drugs called immune checkpoint inhibitors ," says Dr. Weroha. "This drug is designed to release the brakes on the immune system to allow it to do what it naturally wants: kill things it doesn't like. The hope is that the vaccine combined with the immunotherapy drug will kill a lot of ovarian cancer. It's exciting research."

A screening test may be on the horizon.

There is no screening test for ovarian cancer, but Jamie Bakkum-Gamez, M.D. , a Mayo Clinic gynecologic oncologist, is hoping to change that. She and her research team discovered that methylated DNA markers could be used to identify endometrial cancer through vaginal fluid collected with a tampon. Eventually, this same science could extend to ovarian cancer.

Methylation is a mechanism cells use to control gene expression — the process by which a gene is switched on in a cell to make RNA and proteins. When a certain area of a gene's DNA is methylated, the gene is turned off or silenced, indicating that a gene is a tumor suppressor. The silencing of tumor suppressor genes is often an early step in cancer development and can suggest cancer.

Dr. Bakkum-Gamez and her colleagues developed a panel of methylated DNA markers that could distinguish between endometrial cancer and noncancerous tissue in vaginal fluid. Based on this research, she hopes to develop an affordable tampon-based home screening test for endometrial, ovarian and cervical cancers, as well as high-risk HPV .

"This is exciting because this type of screening test can be used by people living in rural areas,” says Dr. Weroha. “If it's successful, it could help healthcare professionals identify ovarian and other gynecologic cancers sooner, when they're more treatable, in people living in all the communities we serve.”

A gynecologic oncologist and clinical trials can help you get the best possible treatment.

If you've been diagnosed with ovarian cancer, Dr. Weroha recommends making an appointment with a gynecologic oncologist . "A gynecologic oncologist will be up to date on the current treatment recommendations and the management of side effects. That's important," he says. "Once the plan is set, however, any medical oncologist could implement it.”

Dr. Weroha also recommends newly diagnosed patients ask their care teams if they are candidates for PARP inhibitors, mirvetuximab or clinical trials. "PARP inhibitors and mirvetuximab are newer treatments that could influence the outcome of your overall treatment. Always ask about clinical trials because when ovarian cancer recurs, there is no treatment so good that we can stop looking for something better," he says. "There is a very realistic hope that if your cancer were to come back, we would have something better that we don't have today."

Learn more about ovarian cancer and find a clinical trial at Mayo Clinic.

Join the Gynecologic Cancers Support Group on Mayo Clinic Connect , an online community moderated by Mayo Clinic for patients and caregivers.

Join the next virtual Gynecologic Cancer Support Meeting: Women of S-Teal . Monthly meetings are held every second Monday from 5:30 to 6:30 p.m. ET.

Also, read these articles:

• A step toward detecting endometrial cancer earlier
• Harnessing the immune system to fight ovarian cancer
• Life after ovarian cancer: Coping with side effects, fear of recurrence, and finding support
• New surgical method for ovarian cancer lights up lesions
• Is a cancer clinical trial right for me?
• New chemotherapy approach for late-stage cancers

Related Posts

Dr. Brad Nitzsche explains why there isn't a universal screening program for ovarian cancer and the symptoms to watch for.

Dr. Maria Linnaus discusses the link between obesity and cancer risk and how bariatric surgery may reduce that risk.

Dr. Kristina Butler discusses health disparities in cancers of the ovaries, uterus, cervix, vulva and vagina and makes recommendations for prevention.

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Preclinical study explores approved drug for ovarian cancer

By alan dove weill cornell medicine.

An iron-binding drug that is already approved for treatment of other diseases could provide a novel way to attack ovarian tumors, according to a new study led by Weill Cornell Medicine researchers.

The preclinical study, which combined the analysis of human ovarian tumors and animal models of the disease, was published July 29 in Cancer Discovery, a journal of the American Association for Cancer Research.

Iron is essential for multiple cellular processes, so actively multiplying cancer cells often need larger amounts of it than normal cells. That’s especially true in ovarian cancers.

“We thought that was a perfect opportunity to try a new approach, because there is an FDA-approved iron-chelating drug called deferiprone that has been successfully used for other diseases with abnormal iron accumulation,” said senior author Juan Cubillos-Ruiz, the William J. Ledger, M.D., Distinguished Associate Professor for Infection and Immunology in Obstetrics and Gynecology at Weill Cornell Medicine. Iron-chelating drugs bind tightly to iron, preventing cells from using it.

To confirm the importance of iron in ovarian cancer, Cubillos-Ruiz’s team first looked at a collection of human tumor samples they’ve amassed over the past decade and analyzed public genomic datasets from ovarian cancer patients with the help of an international team of collaborators. 

“We can isolate different components of tumors from ovarian cancer patients, and study their molecular processes,” said Cubillos-Ruiz, who is also co-leader of the Cancer Biology Program in the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine. The scientists found that ovarian cancer cells demonstrate increased expression of iron-related genes, which correlated with poor patient prognosis. The investigators also found that fluid surrounding ovarian tumors contain high iron content that is readily available to cancer cells. 

The investigators next looked at animal models of the disease.

“We have advanced mouse models of metastatic ovarian cancer that are immunocompetent, so this allows us to study the immune system response in the disease, which is a crucial component,” Cubillos-Ruiz said. Previous iron-related studies have used mice with compromised immune systems, precluding the understanding of how different therapies affect immune responses to tumors. 

The investigators found that the mice recapitulated the disease features quite well: As ovarian cancer progressed, there was more iron accumulation in the tumor, and the cancer cells selectively over-expressed the iron-related gene signatures.

In the animals, deferiprone treatment worked even better than cisplatin, the current standard for ovarian cancer chemotherapy, and functioned directly inside the cells. “We demonstrated that deferiprone can chelate iron in ovarian cancer cells, in vivo,” said lead author Tito Sandoval, a former postdoctoral fellow in Cubillos-Ruiz’s lab.

“We found that combining cisplatin and deferiprone markedly extended the survival of mice with metastatic ovarian cancer, working synergistically compared with the monotherapies,” said Sandoval, who is now a senior scientist in radiation oncology at Washington University School of Medicine in St. Louis. “So, we decided to identify the mechanisms behind this effect.”

The team found that by starving cancer cells of iron, deferiprone triggers a cellular stress response, which prompts the immune system to attack them. Cisplatin affects cancer cell DNA replication, so the two drugs appear to be complementary.

Cubillos-Ruiz is now working with clinical collaborators to design human trials of the new approach. Though deferiprone is already approved for treating other conditions, he emphasized that the team still needs to determine the best way to use it against ovarian cancer. “We want to maximize the potential therapeutic effects, so the clinical trial design is critical,” he said.

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see profile for  Juan Cubillos-Ruiz .

Alan Dove is a freelance writer for Weill Cornell Medicine.

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Precision Oncology via Artificial Intelligence on Cancer Biopsies

A new AI protocol bypasses genomic sequencing and promises access and equity in cancer care

• Joseph McClain - [email protected]

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• Miles Martin - [email protected]

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• Artificial Intelligence
• Breast Cancer
• Ovarian Cancer

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A new generation of artificial intelligence (AI) tools designed to allow rapid, low-cost detection of clinically actionable genomic alterations directly from tumor biopsy slides has been developed by a team led by engineers and medical researchers at University of California San Diego.

A paper describing the new AI protocol for examining routine biopsies, called DeepHRD, was recently published in the Journal of Clinical Oncology .

Senior author Ludmil Alexandrov, Ph.D., professor of bioengineering and professor of cellular and molecular medicine at UC San Diego, says the new method is designed to save weeks and thousands of dollars from clinical oncology treatment workflows for breast and ovarian cancers.

The team says their work represents an enormous step forward in the global efforts to eliminate the delays and health inequalities that have confounded the promise of precision medicine for cancer patients. Big picture: To develop new AI tools that can complement or replace the expensive and time-consuming genomic testing required to determine the best first-line cancer treatment specific for each individual patient.

“A cancer patient today can expect to wait crucial weeks after their initial tumor diagnosis for a standard genomic test, resulting in life-threatening delays in treatment,” said Alexandrov. “It is very concerning that high costs and time delays render lifesaving treatment protocols inaccessible for most patients, disproportionately impacting resource-constrained settings.”

At UC San Diego, this work represents a collaboration spanning all across campus, including the Department of Cellular and Molecular Medicine in the UC San Diego School of Medicine, the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering, Institute of Engineering in Medicine, Department of Medicine, and the UC San Diego Moores Cancer Center.

It was the potential of precision oncology to tailor an individual patient’s treatment options that motivated the collaborators, said Erik Bergstrom, Ph.D., lead author of the study and a postdoctoral researcher in Alexandrov’s lab, which bridges bioengineering and medicine.

“Unfortunately, high costs, tissue requirements and slow turnaround times have hindered the widespread use of precision oncology, leading to suboptimal — potentially detrimental — treatment for cancer patients,” Bergstrom said. “We wanted to see if we could develop a completely different approach to resolve this serious issue by designing AI to circumvent the need for genomic testing.”

“This AI approach saves the patient critical time. Oncologists can prescribe treatment immediately after initial tissue diagnosis. Remarkably, the AI test has a negligible failure rate, while current genomic tests have a failure rate of 20 to 30 percent, necessitating re-testing, or even invasive re-biopsy.”

Bergstrom said the collaborators focused on leveraging the minimum amount of patient information that is available early in the diagnostic process. He explained that virtually every cancer patient undergoes a tumor biopsy, a tissue sample that is routinely processed and examined through a light microscope. The process was developed in the late 19th century and is still the standard backbone of early clinical oncology workflows today.

“Our AI, applied directly to a traditional tissue slide, allows accurate, instantaneous detection of cancer genomic biomarkers,” Bergstrom said. He explained that the team focused on AI identification of a specific biomarker for homologous recombination deficiency (HRD), a condition in which a cancerous cell loses a specific DNA damage repair mechanism.

Bergstrom pointed out that patients with ovarian or breast cancers harboring HRD generally respond well to platinum and PARP (poly-ADP ribose polymerase) therapies, two common forms of chemotherapy.

“This AI approach saves the patient critical time,” Alexandrov added. “Oncologists can prescribe treatment immediately after initial tissue diagnosis. Remarkably, the AI test has a negligible failure rate, while current genomic tests have a failure rate of 20 to 30 percent, necessitating re-testing, or even invasive re-biopsy.”

The study’s co-senior author Scott Lippman, M.D., UC San Diego distinguished professor of medicine, Center for Engineering and Cancer, and Moores Cancer Center member , said the new technology will remove barriers of time and money to allow immediate, universal access and equality to actionable genomic biomarker detection — required for precision therapy — for people with advanced cancers. The extraordinary aspect of this breakthrough AI, is that it will benefit highly-informed, -resourced populations, and remarkably, will close the severe disparities ‘gap’ in precision medicine, especially in resource-constrained, remote regions worldwide where testing is not yet extant.

“The era of precision oncology took off in the late 90s, but recent U.S. studies show that the vast majority of cancer patients are not getting FDA-approved precision therapy,” Lippman said. “And the prime reason is because they're not getting tested. As a clinical oncologist — and I've been doing this for nearly 40 years — there is no question that this approach is the future of precision oncology.”

The AI technology behind DeepHRD is protected by provisional patents through UC San Diego, which have been licensed to io9, a company with strong involvement by Alexandrov, Bergstrom and Lippman, and the goal to move this AI platform into the clinical arena as quickly as possible to make precision therapy real for patients with cancer by getting them onto the precise treatments they need faster. The authors expect that the same technology could be applied to most other genomic biomarkers and many forms of cancer.

Affiliations: The authors have the affiliations noted above: Ludmil B. Alexandrov has appointments at UC San Diego Moores Cancer Center, School of Medicine Department of Cellular and Molecular Medicine, Sanford Stem Cell Institute and the Department of Bioengineering at the Irwin & Joan Jacobs School of Engineering. Erik N. Bergstrom is affiliated with Moores Cancer Center and Department of Cellular and Molecular Medicine. Scott M. Lippman has appointments at Moores Cancer Center, Department of Medicine; and is a Member & Board of Advisors and Co-director of the Center for Engineering and Cancer, Institute of Engineering in Medicine. Other co-authors are Ammal Abbasi and Marcos Díaz-Gay, both of Moores Cancer Center and Department of Cellular and Molecular Medicine and the Jacobs School of Engineering Department of Bioengineering; Loïck Galland and Sylvain Ladoire, both of the Department of Medical Oncology and the Platform of Transfer in Biological Oncology Centre, Georges-François Leclerc Cancer Center and University of Burgundy-Franche, France.

Funding: This work was funded by U.S. National Institutes of Health grants R01ES032547 and U01DE033345 to Ludmil B. Alexandrov, and P30 CA023100 to Scott M. Lippman, as well as by a Curebound Targeted grant and UC San Diego start-up funding to Alexandrov. The research in this study was also supported by UC San Diego Sanford Stem Cell Institute.

Competing interests: Ludmil B. Alexandrov is a compensated consultant and has equity interest in io9, LLC. His spouse is an employee of Biotheranostics, Inc. Scott M. Lippman is a co-founder and has equity interest in io9, LLC. Erik N. Bergstrom is a compensated consultant and has equity interest in io9. Ammal Abbasi and Ludmil B. Alexandrov declare U.S. provisional patent application filed with UCSD with serial numbers 63/366,392 for detecting homologous recombination deficiency from genomics data. Ludmil B. Alexandrov, Scott M. Lippman, and Erik N. Bergstrom declare U.S. provisional patent application filed with UCSD with serial numbers 63/269,033 for artificial intelligence architecture for predicting cancer biomarkers. All other authors declare they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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A New Study Just Linked Endometriosis With A Higher Chance of Ovarian Cancer. Experts Explain The Real Risk

"You are not helpless. In fact, you are empowered now."

Still, endometriosis impacts more than 11 percent of women of reproductive age, making this a topic that a lot of people are paying attention to.

Naturally, these findings are raising a lot of questions about ovarian cancer, endometriosis, and what to do if you have the condition. Here’s what experts say you should know.

Meet the experts: Steve Vasilev, MD , an integrative gynecologic oncologist and medical director of Integrative Gynecologic Oncology at Providence Saint John's Health Center. Jennifer Wider, MD , a women's health expert. Christine Greves , MD, an ob-gyn at the Winnie Palmer Hospital for Women and Babies in Orlando, Florida.

What did the study find?

The study, which was published on July 17 in JAMA , analyzed data from nearly 500,000 women in Utah between the ages of 18 and 55. The researchers specifically looked at how many women were diagnosed with endometriosis, as well as how many were diagnosed with ovarian cancer between 1992 and 2019.

The researchers found that women with endometriosis had a higher risk of developing ovarian cancer than those who don’t have the condition, but the exact level of risk varied by type of endometriosis.

Women with severe types of endometriosis—which include ovarian endometriomas, deep infiltrating endometriosis, or both—had an overall ovarian cancer risk that was about 9.7 times higher than women without the condition. These women also had nearly 19 times the risk of developing type I ovarian cancer, which grows more slowly than other forms, the researchers noted in the study.

What are the study’s limitations?

The study has some shortcomings. One is that the diagnosis of endometriosis was made based on a surgical report—meaning someone had surgery for endometriosis—but that diagnosis may be incorrect without a biopsy. A lot of women who have endometriosis also aren’t properly diagnosed, which can further complicate things.

The study also only relied on medical records in the state of Utah, and some women may have left the state to receive medical care.

What do the findings mean?

The biggest takeaway should be that, while there is an elevated risk, it’s still low. A little over one percent of women in the U.S. will be diagnosed with ovarian cancer over a lifetime, per the National Cancer Institute (NCI). According to NCI estimates, there will be 20,000 new cases of ovarian cancer diagnosed with year, while about 13,000 people will die of ovarian cancer.

It's tricky to apply the risk from the study to the general population. But if the lifetime prevalence of ovarian cancer is 1.2 percent, that means the lifetime risk for women with endometriosis could be 4.8 percent, ob-gyn Jen Gunter, MD, pointed out in her July 22 Substack. For people with deep endometriosis, that would increase to 11.6 percent, Gunter calculated.

But Gunter also noted that there are a lot of unknowns, including when this risk increases and if risk-reducing surgery would help.

What should women with endometriosis do?

It’s important to point out that the study didn’t find that endometriosis causes ovarian cancer—it just found an association. Because of that and because ovarian cancer is a rare disease, the study’s authors don’t recommend that women with endometriosis do anything differently.

But that doesn’t mean this information means nothing—it just needs to be explored more. This is also not the first time that endometriosis has been linked to ovarian cancer. The study “adds substantial evidence to a growing body of research... which indicates a strong association between endometriosis and specific subtypes of ovarian cancer,” says Steve Vasilev, MD , an integrative gynecologic oncologist and medical director of Integrative Gynecologic Oncology at Providence Saint John's Health Center.

“It’s important to understand the findings of the study—the risk may increase for women with ovarian endometriosis and/or deep infiltrating endometriosis—so not everyone with endometriosis,” says women’s health expert Jennifer Wider, MD . “Having said that, if you fall into these categories, you are not helpless. In fact, you are empowered now.”

She recommends talking to your healthcare provider about your risk and getting screened for ovarian cancer if you fall into these high-risk categories.

Vasilev also stresses that “the absolute risk is felt to be very low among the millions of women with endometriosis.”

Christine Greves, MD, an ob-gyn at the Winnie Palmer Hospital for Women and Babies in Orlando, Florida, agrees. “Although this has been discovered, there is still a low risk,” she says. “We recommend that you continue with the recommendation of annual exams and seeing your doctor for any concerns you may have.”

There are a few ways to lower the risk of developing ovarian cancer, no matter your health history. According to the Moffitt Cancer Center , those include:

• Using birth control pills, if appropriate
• Eating a nutritious diet
• Exercising regularly
• Doing your best to maintain a healthy weight
• Avoiding smoking

If you’re considered high risk for ovarian cancer (for example, if you have a certain genetic mutation or a family history of the disease), undergoing a tubal ligation, having a hysterectomy, and having an oophorectomy to remove one or both ovaries may help lower your risk, Moffitt Cancer Center says.

“Yes, there is a small increased risk,” Greves says. She recommends talking to your doctor and, “if you notice you have any changes in your body, bring it up to your ob-gyn.”

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Novel approach to study hypoxia enables identification of a marker for ovarian cancers

by Myreille Larouche, University of Montreal

In a new study, the team led by Étienne Gagnon, Professor in the Department of Microbiology, Infectious Diseases and Immunology at the Université de Montréal and Director of IRIC's Cancer Immunobiology Research Unit, has developed a cell culture protocol that accurately reproduces the characteristic conditions of primary tumors.

The group also identified a novel form of the WT1 protein associated with poor long-term survival in ovarian cancer patients. Published in the journal Cancer Gene Therapy , the study was led by doctoral student Jordan Quenneville.

The LTHY method: To reproduce hypoxic conditions in the laboratory

Hypoxia, a reduced oxygen availability, characterizes the cellular environment of many solid tumors. This characteristic contributes to the resistance of tumor cells to chemotherapy, radiotherapy and immunotherapy. Hypoxia is thus associated with a poor prognosis for patients. However, existing methods for studying hypoxia in the laboratory do not reproduce the conditions observed during tumor development.

To overcome this problem, the Gagnon laboratory team has developed a new cell culture protocol, called LTHY (for "long-term hypoxia"). This method mimics the progressive development of severe hypoxia observed in vivo. The approach developed combines both duration and severity to mimic the appearance and progression of a tumor. This novel protocol is already setting new standards, and several other IRIC groups are beginning to use it in their respective research projects.

A new marker of aggressiveness and survival?

Cells subjected to the LTHY protocol spontaneously undergo an epithelial-mesenchymal transition (EMT), making them invasive and eventually leading to metastasis. At the start of this transition, the cultured cells produce a truncated form of the WT1 protein, known to promote EMT and the development of cancer.

The team also discovered that this new form is derived from an intronic portion of the WT1 gene, a region not normally used for protein production. The resulting product, in addition to being truncated, therefore contains an unconventional protein sequence, known as cryptic. The truncated form of WT1 remains functional and binds to several genes involved in EMT.

Although identified in several human cancer samples, this form of WT1 is particularly present in ovarian cancers, which are known to be hypoxic. Moreover, its presence in this type of cancer is associated with poor long-term survival for patients. Thus, the truncated form of WT1 could become a new marker for predicting aggressiveness and survival in ovarian cancer .

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List of Cancer Types Rising Among Gen Xers, Millennials Reaches 17

Aug. 1, 2024 – The list of cancer types that are more likely to strike young people just grew substantially. Millennials and Generation Xers are now more likely to be diagnosed with 17 types of cancer, compared to Baby Boomers, during early adulthood and middle age. 

The  findings were published Thursday in the journal Lancet Public Health , and the authors warned that the numbers suggest an eventual halt or reversal of decades of progress in cancer rates. They called the reasons for rising cancer rates among young people “poorly understood” but pointed to other research that has linked some cancers earlier in life with obesity, poor diet, environmental impacts, changes in reproductive patterns, and lifestyle factors such as lack of exercise and poor sleep.

While the risk of getting certain cancers rose among young people, the risk of dying from most of those cancers did not follow in lockstep, perhaps pointing toward effective screenings and treatments. But young people were more likely to die of cancers of the gallbladder, testes, colon or rectum, uterus, and (among women only) liver.

“The data highlights the critical need to identify and address underlying risk factors in Gen X and Millennial populations to inform prevention strategies,” said study author Ahmedin Jemal, DVM, PhD, of the American Cancer Society, which partnered with researchers at the University of Calgary in Canada on the project. His comments were part of a  news release .

Specifically, the study examined how common it was for people to be diagnosed with 34 types of cancer, as well as how likely they were to die from most of those cancer types from the year 2000 to 2019. During that time period, there were more than 23 million people in North America diagnosed with those cancers, and more than 7 million deaths.

Five of the 34 cancer types in the study increased at a concerning and steep rate among young people, starting with those born in 1990, compared to people born in 1955. The rates for the following cancer types doubled or tripled every 5 years among young people:

• In men and women: small intestine, kidney and renal pelvis, and pancreatic cancers
• In women: liver and bile duct cancers

Other cancer types flagged for worrying increases among young people included: 

• Estrogen-sensitive breast cancer
• Uterine cancer
• Colorectal cancer
• Gastric and gallbladder and biliary cancers 
• Ovarian cancer
• Testicular cancer
• Anal cancer 
• Kaposi sarcoma (a cancer of the skin and soft tissues)
• Myeloma (a type of blood cancer)
• Oral and pharynx cancers (non-HPV types)

“Because most existing cancer care systems in the USA are not tailored to the unique needs of young adults with cancer, targeted [programs] and services are needed,” the authors wrote, adding that more focus is needed to prevent health risks beginning in childhood, infancy, and even prenatal stages. 

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StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Epithelial ovarian cancer.

Taruna Arora ; Sanjana Mullangi ; Elsa S. Vadakekut ; Manidhar Reddy Lekkala .

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Last Update: May 6, 2024 .

• Continuing Education Activity

Ovarian cancer is a formidable disease characterized by the abnormal growth of cells in the ovaries, often presenting with subtle or nonspecific symptoms in its early stages, leading to challenges in early detection. As one of the deadliest gynecological malignancies, ovarian cancer is typically diagnosed at an advanced stage, complicating treatment and reducing overall survival rates. Various factors, including genetic predisposition, reproductive history, and hormonal factors, contribute to the development of ovarian cancer, underscoring the importance of comprehensive risk assessment and screening strategies.

Engaging with the course content provides invaluable insights into the complexities of ovarian cancer management. Participants learn to proficiently identify risk factors, recognize early signs and symptoms, and navigate the diagnostic and treatment pathways effectively. Moreover, collaborating with an interprofessional team proves instrumental in enhancing patient outcomes, fostering seamless communication and coordination across disciplines. By leveraging the collective expertise of diverse healthcare professionals, a holistic approach to care is ensured, tailoring treatment plans to meet the individual needs of patients. This collaborative effort optimizes therapeutic outcomes, improves quality of life, and empowers patients in their journey against ovarian cancer.

• Differentiate between symptoms of ovarian cancer and those of other gynecological conditions to facilitate early diagnosis and intervention.
• Screen patients for ovarian cancer using appropriate methods, such as pelvic examinations, transvaginal ultrasound, and tumor marker testing.
• Implement evidence-based diagnostic and treatment protocols for ovarian cancer, including biopsy, imaging studies, and multimodal therapy.
• Apply interprofessional team strategies to improve care coordination and outcomes in patients with ovarian cancer.
• Introduction

Ovarian cancers comprise epithelial and nonepithelial ovarian malignancies. Epithelial ovarian cancer is the most prevalent type, accounting for more than 95%, while approximately 5% are nonepithelial ovarian cancers (eg, germ cell, sex-cord stromal, and small cell ovarian cancers). [1]  Epithelial ovarian malignancies are subdivided by histologic classification as diagnostic assessment, management, and patient outcomes can vary based on the subtype, including high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous ovarian cancer.

Ovarian cancer is the leading cause of death in women diagnosed with gynecological cancers and the second most common gynecologic malignancy in the United States, according to the Centers for Disease Control and Prevention. Worldwide, ovarian malignancy ranks as the third most common gynecologic cancer. [2]  Ovarian cancer is also the fifth most frequent cause of death from any cancer in women in the United States and the eighth worldwide. [3] [4] [5]  Ovarian cancer's high mortality is most likely secondary to the disease's nonspecific clinical symptoms and lack of preventative screening methods, which leads to delayed diagnosis; most patients have advanced-stage disease at diagnosis. [1]  The most significant risk factor for ovarian cancer is advanced age, occurring most frequently in women who are postmenopausal. [6]

Evaluation of any ovarian mass primarily consists of clinical assessment, imaging studies, and tumor markers to discern a patient's risk factors for malignancy and characterize the mass; an ovarian cancer diagnosis is histologically confirmed. [7] [8] [9]  Treatment approaches are based on patient factors (eg, comorbidities and previous treatment) and the tumor's stage and histology. Currently, surgical debulking and systemic chemotherapy are typically recommended with or without targeted therapies. Targeted therapy includes antiangiogenic bevacizumab and poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors and immunotherapy. Additionally, neoadjuvant treatment, interval surgical debulking, and heated intraperitoneal chemotherapy are evolving strategies in ovarian malignancy management. [10] [11]  However, despite advances in ovarian cancer treatment, a high recurrence rate and mortality remain a challenge, indicating the need for effective prevention and detection strategies, interprofessional management, and new treatment modalities based on a better understanding of ovarian cancer's molecular characteristics.

Ovarian Cancer Risk Factors 

The etiology of ovarian cancer is not clearly understood; however, several factors have been observed to increase the risk for the development of ovarian malignancy. Risk factors associated with ovarian cancer include:

• Advanced age
• Early onset of menarche
• Late onset of menopause
• Family history
• Nulliparity
• Perineal talc use
• Endometriosis
• Hormone replacement therapy  [6] [12]

Factors that increase ovulation over a lifetime (eg, nulliparity, early menarche, or late menopause) are associated with increased ovarian cancer risk. However, the exact etiologic mechanism is not known. [13]  Additionally, inflammatory conditions (eg, endometriosis and obesity) are thought to lead to the development of ovarian cancer secondary to oxidative stress and deoxyribonucleic acid damage. [14] [15]  A significant risk factor for ovarian cancer is a positive personal or family history of breast or ovarian cancer. Germline mutations in  BRCA1  or  BRCA2  genes are a prevalent underlying cause of malignancy predisposition in individuals. Other hereditary cancer syndromes that also increase the risk for ovarian cancer are associated with other gene mutations, including mismatch repair genes in Lynch syndrome,  tumor protein p53  ( TP53)  in Li-Fraumeni syndrome,  STK11  in Peutz-Jeghers syndrome,  CHEK2 ,  RAD51 ,  BRIP1 , and  PALB2 . [16]  Recent data suggest that high-grade serous ovarian cancer (HGSC) may originate in the fallopian tube based on observed changes in the distal epithelium in fallopian serous tubal intraepithelial carcinoma, an HGSC precursor. [17] [18]  Studies have not found proposed ovarian cancer screening strategies to be effective; still, many organizations have agreed that offering various screening methods to these high-risk patients is appropriate. [7] [17]

Ovarian Cancer Protective Factors 

Factors that reduce ovulation are associated with a decreased risk of ovarian cancer, including:

• Oral contraceptives
• Bilateral tubal ligation or salpingectomy
• Breastfeeding
• Multiparity  [12] [19]  
• Epidemiology

Study results have estimated the risk of a woman developing ovarian cancer in her lifetime up to age 95 to be 1.1%. [7]  In the US, in 2022, approximately more than 19,000 new ovarian cancers were diagnosed, and the number of ovarian cancer deaths was estimated to be more than 12,000. Furthermore, the incidence of ovarian cancer subtypes varies according to age. The incidence of high-grade serous ovarian cancer peaks in women between 60 and 65 years, and the incidence of low-grade endometroid ovarian cancer is highest in women between 45 and 50 years. Clear-cell ovarian cancers are highest in women between the ages of 55 and 60. [3]  The highest incidence of high-grade serous and low-grade endometrioid cancers is in non-Hispanic White women; Asian/Pacific Islander women have a higher incidence of clear cell cancer. Non-Hispanic Black women have the lowest incidence of all ovarian cancer subtypes. [3]

Survival and recurrence rates also vary based on a patient's stage at diagnosis. More than half of patients diagnosed with ovarian cancer have metastasis at presentation. The 5-year survival of early-stage ovarian cancer is 93.1%, compared to 30.8% in advanced-stage disease. The recurrence risk in stage I ovarian cancer is less than 10%, while 90% of women with stage IV ovarian cancer have recurrence. [7]

• Pathophysiology

Ovarian Cancer Dissemination Pattern

The regional lymphatic spread of ovarian cancer follows physiologic lymphatic drainage of the ovaries and fallopian tube most frequently to para-aortic and paracaval nodes first, as well as external iliac, common iliac, hypogastric, and lateral sacral lymph nodes. The most common site for distal ovarian and fallopian metastasis is the peritoneum, including the omentum and visceral surfaces, which are drained by diaphragmatic lymphatic vessels. Hematogenous spread is thought to have a limited role other than in advanced-stage disease, though sparse evidence of a more significant hematogenous contribution exists. [20]

Additionally, results from several studies have demonstrated that high-grade and low-grade serous ovarian cancers may actually originate from the fallopian tube precancerous lesions (eg, tubal intraepithelial neoplasia and endosalpingiosis). Fallopian tube involvement during ovarian cancer staging may appear as a fallopian tube mass within the lumen that is histologically confirmed as a tubal intraepithelial carcinoma, a widespread malignancy with a neoplasm involving the fallopian tube and ovary, or a tubal intraepithelial carcinoma identified histologically during risk-reducing surgery. [21]  Therefore, definitively differentiating whether the primary tumor is ovarian, fallopian, or peritoneal in origin may be difficult. Thus, the International Federation of Gynecology and Obstetrics staging incorporates tumor involvement in all of these sites. [22]  (Refer to the  Staging  section for more information on ovarian cancer staging)

Pathophysiologic Mechanisms of Epithelial Ovarian Cancer

Because the underlying etiologies of ovarian cancer have not been defined, the exact pathophysiologic mechanisms leading to disease are not fully understood. However, genetic mutation is a known pathway. Malignant cellular transformation can occur due to deoxyribonucleic acid (DNA) mutations that occur before (ie, germline) or after (ie, somatic) fertilization. The primary somatic ovarian cancer mutation is  TP53 , which is prevalent in high-grade serous carcinomas. However, the  TP53  gene   is not used as a tumor marker for ovarian cancer because the gene is also found in benign ovarian tissue. Less frequent somatic mutations include  CSMD3 ,  FAT3 ,  BRCA1 ,  BRCA2 ,  PTEN ,  PIK3CA ,  KRAS ,  BRAF ,  CTNNB1 , and  PPP2R1A . [23]  Inherited DNA mutations associated with ovarian cancer include  BRCA1  and  BRCA2, ATM ,  BRIP1 ,  NBN ,  NF1 ,  PALB2 ,  RAD51C , and  RAD51D . Hereditary nonpolyposis colorectal cancer, also known as Lynch syndrome, is associated with mismatch repair mutations in  MLH1 ,  MSH2 ,  MSH6 ,  PMS2 , and  EPCAM  genes that increase the risk of ovarian malignancy. Other inherited syndromes associated with ovarian cancer include Cowden syndrome with a  PTEN  mutation and Peutz–Jeghers syndrome with  STK11  mutations. [18]  

Epigenetic alterations in gene regulation mechanisms, including  DNA methylation, that affect genetic expression are associated with the development of ovarian malignancy and other cancers. Results from a recent study showed evidence of epigenetic methylation alterations in women with early-stage ovarian cancers, though their use as a tumor marker is still under investigation. [23]

• Histopathology

An ovarian cancer diagnosis is histologically confirmed. [9]  Epithelial ovarian malignancies are typically subdivided by histologic classification as clinical behavior, management, and outcomes vary based on the subtype. Classification comprises cytology analysis, immunohistochemical markers, and molecular studies. The primary ovarian cancer subtype classifications are high-grade serous, low-grade serous, clear cell, endometrioid, and mucinous ovarian disease. [24]  Transitional cell ovarian carcinomas were previously classified as a distinct histologic subtype also; however, several studies demonstrated that these tumors were similar to high-grade serous ovarian cancer. Therefore, transitional cell ovarian tumors are classified within the high-grade serous histologic subtype. [25]  Rare histologic ovarian cancer subtypes include carcinosarcomas, malignant Brenner tumors, and undifferentiated carcinomas. [24] [25]  Additionally, tumor grading for nonserous epithelial ovarian cancers are based on histologic architecture. In contrast, serous carcinoma grading is based on tumor biology. [21]  The following classification is used for nonserous epithelial ovarian cancer grading:

• GX: Unable to assess grade
• G1: Well differentiated
• G2: Moderately differentiated
• G3: Poorly differentiated  [21]

Immunohistochemical Classification of Epithelial Ovarian Cancers

Immunohistochemical stains are utilized to help differentiate ovarian cancer histological subtypes. The WT1 immunohistochemical marker differentiates high-grade and low-grade serous from clear-cell and mucinous subtypes, as WT1 is absent in clear-cell and mucinous tumors. The p53 abnormal (p53abn) marker can also identify high-grade serous from low-grade tumors. Most endometrioid subtypes are negative for WT1 and positive for p53 wild-type; however, 10% to 15% of endometrioid tumors may be positive for WT1 and p53abn markers. In these cases, molecular testing for  BRCA1  and  BRCA2  homologous repair deficiency in high-grade serous tumors and mismatch repair deficiency (MMRd) in endometrioid tumors can be performed. Immunohistochemical positive stains for napsin A and HNF1B with negative staining for progesterone receptors typically indicate clear cell tumors, whereas converse findings are characteristic of endometrioid tumors. A combination of napsin A negative and progesterone receptor negative stains usually identifies mucinous ovarian carcinomas. Any vimentin staining indicates an endometrioid neoplasm. Rare ovarian cancer subtypes may be identified by other immunohistochemical markers, including undifferentiated carcinomas, identified by absent ARID1B, BRG1, or INI1 staining. Serous tubal intraepithelial carcinoma is characterized by p53 and Ki-67 markers on histologic examination. [6] [23] [24]

High-Grade Ovarian Serous Cancer Histologic Characteristics

High-grade serous carcinoma is the most common subtype of ovarian carcinoma. [6]  Characteristic histologic findings of high-grade serous cancer include architectural papillary and solid growth, significant nuclear atypia, hyperchromatic nucleoli, and increased mitotic activity (more than 12 per 10 high-powered field). [1]  In 96% of high-grade serous subtypes, molecular testing demonstrates a  TP53  mutation. Other findings from molecular studies include high copy number alterations and  BRCA1  or  BRCA2  germline mutations. [6]  

Low-Grade Ovarian Serous Cancer Histologic Characteristics

Low-grade serous subtypes account for approximately 10% of epithelial ovarian cancers. They are typically differentiated from high-grade serous cancers due to converse cytologic findings, including small papillae with uniform nuclei and little mitotic activity. Hyalinized stroma and psammoma bodies are frequently observed also. Molecular testing findings of  BRAF  and  KRAS  mutations are commonly seen in low-grade serous ovarian cancers. [6]

Endometrioid Ovarian Cancer   Histologic Characteristics

Approximately 10% of epithelial ovarian cancers are endometrioid subtypes. Histologically, these tumors are similar to endometrial endometrioid cancer with round or back-to-back complex, cribriform, or villous glands. Mutations seen in molecular studies include  CTNNB1, PIK3CA ,  ARID1A ,  KRAS ,  PTEN , and  PPP2R1A. [6]   Additionally, the  POLE  mutated, MMRd, no specific molecular profile, and p53abn molecular subtypes used to classify endometrial cancer are also observed in endometrioid ovarian cancers and can be utilized to determine prognosis similarly. [24]  See StatPearls' companion reference, " Endometrial Cancer ," for more information on endometrial cancer molecular subtypes.

Clear-Cell Ovarian Cancer Histologic Characteristics

Ovarian clear-cell carcinomas are less prevalent and account for less than 5% of ovarian carcinomas. Histopathologically, they may have tubules, solid areas, and complex papillae with cellular clearing, cystic growth pattern, and a characteristic hobnail growth pattern. Mutations seen in molecular studies typically involve  TP53  or both  ARID1A  and  PIK3CA. [6]  

Mucinous Ovarian Cancer   Histologic Characteristics

Approximately 2.4% of epithelial ovarian cancers are classified as a mucinous subtype. Typically, this subtype has a more favorable prognosis compared to serous ovarian cancers because 80% of mucinous ovarian carcinomas are diagnosed at earlier stages, commonly stage I. Mucinous ovarian carcinomas are often heterogeneous, where a mixture of elements, including benign and malignant tumors, are found in a single specimen. This ovarian cancer subtype is similar to gastrointestinal tract malignancies as complex glandular cytology with architectural features of adenocarcinoma are typically noted on histologic examination. The amount of stromal invasion varies. [1] [26]  Because distinguishing primary ovarian mucinous carcinomas from metastatic mucinous appendix tumors is difficult due to their close association, many gynecologic oncologists practice routine appendectomy in patients with ovarian mucinous carcinomas. [27]   KRAS  mutations are the most frequent molecular alterations identified in mucinous ovarian cancer subtypes. Less frequently, other gene mutations, including  HER2 ,  CDKN2A , and  TP53 , are found in molecular studies for this subtype. [1] [24]

• History and Physical

Clinical History

Epithelial ovarian cancers occasionally may be detected incidentally in patients who are asymptomatic; however, most patients present with nonspecific symptoms, including abdominal fullness, bloating, nausea, abdominal distention, early satiety, fatigue, change in bowel movements, urinary symptoms, back pain, dyspareunia, and weight loss. [26]  Abnormal uterine bleeding is not a common ovarian cancer symptom. [22]  Furthermore, early-stage disease is typically asymptomatic or mild and easily dismissed. Hence, ovarian carcinoma symptoms are frequently missed at an early stage as the symptoms can be attributed to other possible disease processes. Because managing adnexal masses involves risk stratification, a thorough clinical history should be obtained, including a patient's personal and family medical history, hereditary cancer risk assessment, and a review of symptoms. [18] [27]

Physical Examination

A thorough physical examination, including pulmonary auscultation, breast and abdominal palpation, and rectovaginal examination on an empty bladder, should be done to look for pelvic and abdominal masses. Lymph nodes should be palpated, including the cervical, supraclavicular, axillary, and groin areas. The pelvic examination should visually inspect the perineum, cervix, and vagina, in addition to a bimanual examination. Irregular, firm, fixed, and nodular masses or ascites should prompt further evaluation with imaging studies. [7]  A palpable pelvic mass, ascites, or diminished breath sounds due to pleural effusions may also be found in advanced cases. Rarely is a firm umbilical or paraumbilical nodule (ie, Sister Mary Joseph nodule) palpable due to metastasis. Lesar-Trélat sign, which refers to a sudden increase in the finding of seborrheic keratosis, also gives a clinical clue indicating the presence of occult cancer. [28]

Paraneoplastic syndromes can be infrequently associated with ovarian cancer. Subacute cerebellar degeneration due to tumor-induced autoimmune reactivity against cerebellar antigens can lead to symptoms like ataxia, dysarthria, nystagmus, vertigo, and diplopia. This condition commonly precedes the occurrence of the primary ovarian tumor in months or years. Trousseau syndrome has also been associated with ovarian cancer. Increased levels of circulating parathyroid hormone-releasing protein can lead to hypercalcemia, which can manifest as altered mental status, fatigue, constipation, abdominal pain, and increased thirst and urinary frequency. Such early warning signs of various paraneoplastic syndromes should be considered well in advance to avoid the diagnosis of ovarian cancer directly at an advanced stage where the patient may not be amenable to curative therapy. [28] [29]

Laboratory Studies and Biomarkers

Serum laboratory testing should typically include a complete blood count and metabolic profile. [7]  The American Society of Clinical Oncology guidelines recommend offering genetic testing for  BRCA1  and  BRCA2  to all women with epithelial ovarian cancer, and in patients with clear cell, endometrioid, or mucinous ovarian cancer subtypes, MMRd molecular testing should be offered . [30]

Tumor markers are usually measured in conjunction with imaging studies of patients with suspected malignancy. Human gonadotropin, alpha-fetoprotein, and carcinoembryonic antigen tumor markers should be obtained to help exclude germ-cell and gastrointestinal malignancies. [22]  Cancer antigen 125 (CA-125) is a glycoprotein produced by Müllerian epithelium that is detectable by serum laboratory studies and the most recommended biomarker to evaluate suspected ovarian cancer. CA-125 levels are increased in most advanced epithelial ovarian cancer cases but are elevated only in 50% of early-stage disease cases; therefore, the sensitivity of this biomarker is limited. The specificity and positive predictive value are higher in postmenopausal women than in premenopausal women. A CA-125 level greater than 35 U/mL in a woman who is postmenopausal indicates a high malignancy risk. However, CA-125 is not specific to epithelial ovarian cancers as it can also be elevated in patients with other conditions, including pregnancy, nonovarian malignancies, and inflammatory pathologies (eg, acute pelvic inflammatory disease, adenomyosis, and endometriosis). [9]

Human epididymis protein 4 (HE4) is a peptide protease inhibitor found in epididymal epithelium. Though not typically found in ovarian epithelium, HE4 is detected by serum laboratory studies in ovarian cancer tissue with a specificity of 96%. This biomarker is not diagnostic for ovarian cancer, though, as HE4 is also elevated in other malignancies (eg, endometrial cancer and lung adenocarcinomas). HE4 has a higher sensitivity than CA-125 in early-stage ovarian cancers and a higher specificity in late-stage disease. However, CA-125 has a higher sensitivity in late-stage ovarian cancers than HE4. [9]  

Various diagnostic formulas using tumor markers have been proposed to calculate the risk of epithelial ovarian cancer. CA-125 levels are used to calculate the malignancy index (RMI) risk. The RMI is a multiple of CA-125, transvaginal ultrasound parameters, and menopausal status to determine the risk of an adnexal mass being an ovarian malignancy. [28]  An RMI, particularly in postmenopausal women, higher than 200 is associated with a high risk of malignancy, with a specificity of more than 96%. [28]  The risk of ovarian malignancy algorithm (ROMA) utilizes a mathematical formula that incorporates HE4 and CA-125 levels adjusted for premenopausal and postmenopausal status to determine the risk of malignancy. [31]  However, these formulas are less effective in predicting the malignancy of an adnexal mass than risk stratification systems based on imaging studies. [9]

Other investigated biomarkers include folate receptor alpha, CA72-4, transthyretin, CA15-3, and glycodelin. CA-125 remains the most beneficial and commonly used tumor marker for evaluating ovarian cancer risk. However, these other tumor markers may have more utility when combined with CA-125. [9]

Transvaginal Imaging 

Transvaginal ultrasound is the preferred initial imaging modality to characterize an adnexal mass due to the ability to visualize differentiating features between benign and malignant disease. Findings consistent with ovarian cancer include papillary or solid components, irregularity, ascites, and high-color Doppler flow. However, 20% of patients with an adnexal mass have equivocal findings, in which case additional imaging, typically with magnetic resonance imaging (MRI), is recommended. [32] [7]  Predicting if an adnexal mass is malignant can be complex. Overdiagnosing an ovarian mass can lead to unnecessary interventions and psychological harm; however, a missed cancer diagnosis may result in increased patient morbidity and mortality. The Ovarian-Adnexal Reporting and Data System (O-RADS) ultrasound risk stratification system helps clinicians make management decisions, primarily when referral to an oncology specialist is indicated, for average-risk patients based on ultrasound findings. [32] [33]  O-RADS stratifies adnexal masses into the following categories based on established characteristics:

• O-RADS 0 : Transvaginal ultrasounds that have inadequate visualization due to technical factors (eg, bowel gas, adnexa, or patient intolerance) are placed in this category. Typically, an ultrasound should be repeated, or another imaging modality should be utilized. [33]
• O-RADS 1 : Physiologic adnexal lesions with no abnormal findings (eg, follicles and corpus luteums) are classified as O-RADS 1; however, it only applies to those who are premenopausal. No additional management or imaging follow-up is indicated, as these lesions have a 0% risk of malignancy. [33]
• O-RADS 2 : This category indicates a less than 1% risk of malignancy; therefore, masses are most likely benign. Characteristics of lesions in this category include simple cysts or unilocular cysts with internal echos but smooth walls, sized less than 10 cm. Typical hemorrhagic cysts, dermoid cysts, endometriomas less than 10 cm or paraovarian cysts, peritoneal inclusion cysts, and hydrosalpinx of any size without any suspicious features are also included in this category. Specific management (eg, specialist consultation, additional imaging studies, or continued surveillance) is based on clinical features, including lesion size, type of lesion, and patient's menopausal status. [33]
• O-RADS 3 : Adenexal lesions within this category have a 1% to less than 10% risk of malignancy. The same lesions included in the O-RADS 2 category (eg, simple cysts and unilocular cysts) but 10 cm and larger in size are classified as O-RADS 3. Additionally, unilocular cysts with irregular walls, multilocular cysts without a solid component smaller than 10 cm and absent to moderate color Doppler flow, and avascular solid-appearing masses of any size are also placed in this category. The management of lesions in this category usually involves a gynecology clinician. An MRI examination may be considered based on clinical suspicion. [33]
• Multilocular cysts that are  larger than or equal to 10 cm
• Multilocular cysts with an irregular inner wall or septal irregularity (less than 3 mm in height)
• Unilocular and multilocular cysts with a solid component or significant color Doppler flow of any size
• Unilocular cysts with 1 to 3 papillary projections of any size or color Doppler flow
• Smooth solid lesions with mild to moderate color Doppler flow  [33]
• Irregular solid lesions of any size or color Doppler flow
• Smooth solid lesions of any size with high-color Doppler flow
• Unilocular cysts with 4 papillary projections or more of any size or color Doppler flow
• Multilocular cysts of any size with a solid component and high-color Doppler flow
• Ascites or peritoneal nodules except when associated with physiologic cysts or a benign lesion (ie, O-RADS 2)  [33]

Magnetic Resonance Imaging 

Based on ultrasound imaging, up to 31% of adnexal masses fall within an indeterminate risk category. In patients with equivocal transvaginal ultrasound findings or a CA-125 within normal range, MRI may help further characterize an adnexal mass because of a high specificity when identifying malignancies. [34]  Similar to the ultrasound O-RADS stratification method, the Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI), also referred to as the AdnexMR Scoring system, classifies the malignancy risk of an adnexal mass into 5 categories based on MRI features. The main purpose of this stratification is to help guide preoperative decisions, including surgical necessity and extent; however, trials are still underway to establish management recommendations for each risk group. [32] [35] [36]

The recommended technique for MRI consists of precontrast axial T1-weighted and T2-weighted images with and without fat suppression, dynamic sequence postcontrast T1-weighted images, followed by perfusion-weighted and diffusion-weighted sequences if an adnexal mass was visualized with T1-weighted and T2-weighted images. A slice less than or equal to 3 mm thickness for the T2-weighted and contrast-enhanced T1-weighted images is recommended. [32] [35]  O-RADS MRI stratifies adnexal masses into the following categories based on specific criteria: [32]

• AdnexMR 1 : No adnexal lesion is visualized.
• AdnexMR 2 : Characteristics of these lesions are considered benign. The established features of this category include purely adnexal cystic, endometriotic, or fatty masses with no wall enhancement or solid tissue or solid masses with a low homogenous signal on the T2-weighted and the high b-value diffusion-weighted images.
• AdnexMR 3 : These lesions are likely benign. Characteristic features include unilocular cysts with an irregular enhancing wall and multilocular cysts with simple, proteinaceous, hemorrhagic, or endometriotic fluid, not including purely cystic, endometriotic, and fatty masses. Additionally, dynamic perfusion time-intensity curve type 1 solid masses are classified in this category.
• AdnexMR 4 : These lesions have an indeterminate risk of being malignant. Dynamic perfusion time-intensity curve type 2 solid masses define this group.
• AdnexMR 5 : Masses in this category have a high risk of malignancy. Dynamic perfusion time-intensity curve type 3 solid masses, peritoneal implants, or omental thickening or nodules are characteristic features of these lesions. [35]

Computed Tomography Imaging

Computed tomography (CT) scans are frequently performed before MRI to evaluate differential diagnoses in patients with nonspecific symptoms. However, MRI is recommended as a second-line modality following ultrasound as it is more effective in visualizing ovarian malignancies. Nevertheless, CT imaging of the abdomen, pelvis, and thorax is commonly performed to evaluate the extent of disease and for preoperative planning due to the increased availability of this modality. [37]  For instance, extensive lymph node involvement can be a contraindication to surgery in select patients. Positron emission tomography-CT may be considered to determine lymph node involvement as this modality is more beneficial than CT alone in evaluating lymph node and peritoneal metastases and recurrent disease. [38]

• Treatment / Management

Approach to Epithelial Ovarian Cancer Management

Though 90% of women with early-stage disease of any grade are cured with treatment, most patients are diagnosed at an advanced stage, which underlines the necessity for prompt detection and specialist treatment. Determining the best management approach for each patient, including the sequence of surgical and systemic therapy, is individualized based on tumor stage and biology, previous treatment, and coexisting conditions. Generally, surgical therapy is the initial treatment performed in most patients with epithelial ovarian cancer for histologic confirmation, staging, and tumor debulking, which will help guide adjunct treatments. Some patients with advanced-stage disease that is unlikely to be completely resected or unresectable may benefit from undergoing neoadjuvant chemotherapy before surgical cytoreduction. In younger patients with stage I and low-grade ovarian cancers who desire fertility-sparing surgery, surgical staging with uterine preservation may be considered. Therefore, clinicians must consider various management approaches in the treatment of ovarian cancer. [1] [37]

Staging and Primary Debulking Surgery

Ovarian cancer is surgically staged using the FIGO and tumor, node, metastasis (TNM) grading system. (Refer to the  Staging  section for more information on ovarian cancer staging). Evidence demonstrates that chemotherapy is more effective and improves the overall prognosis in patients with optimal surgical staging. Because primary surgical staging and debulking are so critical to patient outcomes, the procedure should be performed by an experienced gynecologic oncologist in a facility with the necessary equipment available. Surgical staging typically comprises a midline laparotomy with abdominal and pelvic exploration, ascites or peritoneal washing collection, total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymph node evaluation, peritoneal biopsy, and omentectomy. Optimal surgical debulking resects all grossly visible disease to reduce tumor burden to the greatest extent, particularly in epithelial ovarian cancer subtypes less affected by chemotherapy (eg, low-grade serous, clear cell, and mucinous carcinoma). [1]  In patients with stage III disease or greater, cytoreduction to less than 1 cm should be performed if complete resection is not possible; more extensive procedures may also be involved, including bowel and diaphragm resection and upper abdominal exploration. Routine pelvic and paraaortic lymphadenectomy is not recommended by the American Society of Clinical Oncology (ASCO), but enlarged lymph nodes should be excised. However, some professional societies (eg, the European Society for Medical Oncology) do recommend systematic pelvic and paraaortic lymphadenectomy for high-grade disease. [1] [37] [39]

In patients with ovarian cancers that appear to be low-risk and early-stage wishing to retain fertility options, fertility-sparing surgical therapy may be considered. Clinicians should refer these patients to a reproductive endocrinologist for preoperative consultation. The National Comprehensive Cancer Network (NCCN) states that fertility-sparing modifications to standard debulking surgery can include retention of the uterus and contralateral ovary and fallopian tube or solely preserving the uterus, depending on tumor stage and histology. However, surgical staging procedures should still be performed to exclude occult disease. Any patient who may be considering fertility-sparing surgery should be thoroughly counseled on the risks of recurrent ovarian cancer. The NCCN guidelines do not recommend fertility-sparing surgery for any patients with clear-cell ovarian cancers of any stage. [37] [40]

Neoadjuvant Chemotherapy and Interval Debulking Surgery

Neoadjuvant chemotherapy followed by interval debulking surgery may be performed in patients deemed poor surgical candidates or with a low likelihood of optimal cytoreduction. Gynecologic oncologists should evaluate patients with suspected advanced stage IIIC or IV epithelial ovarian cancer to determine if neoadjuvant chemotherapy would be effective in decompressing the tumor burden to increase the likelihood of optimal cytoreduction. [1] [37]  Before administering neoadjuvant chemotherapy, patients should carry a histological diagnosis of invasive ovarian cancer confirmed by biopsy, preferred over specimens obtained from fine-needle aspiration of paracentesis. [41]  

Various clinical trials have compared neoadjuvant chemotherapy with interval cytoreduction surgery versus primary cytoreductive surgery. These trials have shown overall survival is the same between patients who underwent primary cytoreduction and those who had neoadjuvant chemotherapy; however, neoadjuvant therapy may reduce complications, including the necessity of bowel resection and stoma formation. [42]  Other trials are still investigating which treatment approach is most effective. Therefore, interprofessional consultation, including gynecologic oncologists, should individualize treatment decisions based on clinical factors when determining the optimal treatment approach. [6] [43]  In patients who do undergo neoadjuvant chemotherapy, the tumor is reassessed with imaging to determine resectability after 3 to 4 cycles of chemotherapy. [6] [43]  If tumor progression is observed during neoadjuvant chemotherapy, interval debulking surgery is not recommended, as studies have not demonstrated any survival benefit. Enrollment in clinical trials or treatment cessation and beginning end-of-life care may be considered in these patients. [37]

Adjuvant Chemotherapy

Following primary debulking surgery, adjuvant chemotherapy decisions should be guided by surgical staging as disease characterization may change following surgical assessment, eg, upstaging patients thought to have early-stage disease. Stage I grade 3, stage IC and II, high-grade, and clear cell ovarian cancers are at high risk for recurrence; stage IA or IB grade 1 endometrioid, serous, or mucinous ovarian cancers are at low risk for recurrence. In low-grade early-stage disease, adjuvant chemotherapy does not improve overall survival. Therefore, though optimal primary cytoreduction alone may treat low-risk early-stage ovarian cancers, high-risk early-stage disease benefits from adjuvant chemotherapy; furthermore, stage I ovarian cancers that are inadequately staged or suboptimally resected should also be administered adjuvant chemotherapy if additional surgery is unable to be performed. A combination of carboplatin and paclitaxel are the most commonly used agents, though recommendations regarding agents, dosage, or duration have not been established. For advanced-stage disease, chemotherapy regimens, including the administration mode, are determined based on the presence of residual disease. (Refer to the  Medical Oncology  section for more information on chemotherapy). [22] [37] [44]

Hormone Therapy

In patients with recurrent and metastatic low-grade serous ovarian cancer, some studies have shown evidence of clinical benefit with hormonal therapy. A study comparing patients who received adjuvant hormonal therapy following primary debulking surgery and platinum-based chemotherapy and patients who were only observed revealed that progression-free survival was significantly longer in those receiving adjuvant hormonal therapy. However, other studies have not shown a significant difference between adjuvant hormonal therapy and other treatments. [21]  Some experts suggest adjuvant therapy (eg, aromatase inhibitors, tamoxifen, or luteinizing hormone-releasing hormone agonists) may be considered to help decrease the rate of tumor growth in ovarian tumors with estrogen or progesterone receptors. [39]

Maintenance Therapy

NCCN guidelines recommend observation with continued surveillance in patients with stage I disease. However, those with stage II to IV ovarian cancer have a high risk of disease recurrence within 5 years. Because of this, maintenance therapy is frequently employed to reduce recurrence risk by ensuring the effective killing of residual slowly dividing cells by decelerating the cell turnover so that the dormant population of cancer cells does not progress to grow enough to be detected by either elevation of biomarkers or clinical evidence of recurrent disease. [45]

Among various maintenance therapy options, targeted therapies are evolving in this realm of ovarian cancer treatment. Initially, targeted therapy was utilized in the treatment of recurrent ovarian cancer. More recently, studies demonstrated that in patients who had a good response to adjuvant chemotherapy, targeted molecular therapies used in maintenance treatment demonstrated efficacy in improving progression-free survival, especially in patients with high-risk disease. Anti-angiogenic agents and PARP inhibitors have been the most studied targeted therapy agents. [46] [43]  Several randomized maintenance therapy trials have been performed that compared the effectiveness of various agents. Based on current studies, most recommendations state that the disease stage, the primary systemic therapy used, the tumor response, and  BRCA1  and  BRCA2  mutation status should guide maintenance therapy decisions. Options for maintenance therapy include:

Platinum-based chemotherapy agents

In patients who demonstrated a good response following primary cytoreduction and chemotherapy, clinical discretion previously guided the decision to initiate maintenance therapy as evidence from several studies showed increased toxicity with no significant improved overall survival with its use. The phase 3 randomized trial, GOG-178, evaluated patients diagnosed with stage III to IV ovarian cancer, comparing the outcomes of 2 maintenance therapy durations following complete clinical response to platinum/paclitaxel therapy: 12 months versus 3 months of paclitaxel maintenance therapy. After 50% accrual interval analysis, improved progression-free survival was seen favoring the extended therapy cohort. However, the study closed early. A follow-up study later showed no overall survival benefit compared to the same maintenance monotherapy for 22 months versus 14 months. [47]  Another trial, GOG-175, showed no significant difference in 5-year survival or recurrence-free interval where high-risk early-stage ovarian cancer patients were randomized to observational versus weekly paclitaxel 40 mg/m² for 24 weeks after completion of 6 cycles of carboplatin and paclitaxel for 3 cycles. [48]  A 3-arm phase 3 trial following standard chemotherapy, GOG-0212, compared observation without immediate therapy to 12 months of paclitaxel or polyglutamated paclitaxel but showed disappointing results. [49]  Therefore, targeted therapies that are less toxic have replaced chemotherapy as maintenance therapy agents.

Anti-angiogenic inhibitors

Angiogenesis inhibitors are agents that target tumorous vascular growth mechanisms. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has been studied in combination with chemotherapy and was the first anti-angiogenic agent approved in the United States. [43] [46]  In 2 major landmark trials (ICON7 and GOG-0218), patients with advanced-stage ovarian cancer had improved progression-free survival in the maintenance bevacizumab cohort when compared with surveillance only. [50]  Therefore, bevacizumab for maintenance therapy for stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients with a complete or partial response following primary surgical debulking and bevacizumab in combination with carboplatin and paclitaxel, is recommended by the NCCN. However, if bevacizumab is not used during the primary treatment with chemotherapy, the NCCN does not recommend use for maintenance therapy. Additionally, anti-angiogenic inhibitors are not recommended in patients with  BRCA1  and  BRCA2  mutations because other targeted therapies are more effective. In patients with wild-type or an unknown  BRCA1  and  BRCA2  mutation status, bevacizumab is still appropriate. [45]  Conversely, ASCO is more conservative in its recommendation of bevacizumab. Though bevacizumab significantly benefits progression-free survival when used as concurrent therapy followed by single-agent maintenance therapy, no clear clinical benefit in overall survival has been demonstrated; therefore, ASCO merely suggests that it may be considered until more evidence is found. [37]  Other angiogenesis inhibitors include pazopanib, sorafenib, sunitinib, cediranib, and aflibercept; however, these medications are not frequently used due to adverse effects or cost. [1]

Poly(ADP)-ribose polymerase inhibitors

PARP inhibitors have recently gained momentum for the maintenance treatment of ovarian cancer. PARP inhibitor agents include olaparib, niraparib, and rucaparib. Olaparib was the first Federal Drug Administration (FDA)-approved drug in this subgroup indicated to treat advanced  BRCA  mutated ovarian cancer after platinum-based chemotherapy, based on SOLO-1, phase 3 randomized double-blind, placebo-controlled trial. Olaparib reduced disease progression or death by 70% (hazard ratio 0.30, 0.23 to 0.41;  P  < .001). [51]  The PAOLA-1 trial, a phase 3 randomized controlled trial of 806 women with stage III to IV high-grade serous or endometrioid ovarian cancer, showed a progression-free survival benefit of 4.5 months in the group that received olaparib and bevacizumab maintenance versus placebo and bevacizumab. [52]  This combination of olaparib, niraparib, or rucaparib with bevacizumab achieved FDA and NCCN approval as a first-line maintenance treatment for these patients with ovarian cancer after initial platinum-based chemotherapy with partial or complete response or tumors associated with homologous recombination deficiency (HRD) defined by the presence of deleterious  BRCA  mutation. Recent clinical trials include the VELIA and PRIMA trials using a newer PARP inhibitor, veliparib, and niraparib maintenance therapy, respectively, showed markedly improved progression-free survival compared to the placebo group in patients with newly diagnosed advanced-stage ovarian cancer who initially responded to first-line platinum-based chemotherapy. [53] [54]

Immunotherapy

Immunotherapy agents have recently shown significant benefits in treating solid malignant tumors by activating a patient's immune system against tumor cells. However, published data do not show any benefit in patients with ovarian cancers so far. The resulting controversial data diverted the focus on combination strategies involving immune checkpoint inhibitors with PARPs, chemotherapy, anti-angiogenic agents, and more. Combining such therapies shows more anti-tumor activity than concentrating on a single pathway. This promising data is from initial phase trials, and further results from ongoing phase 2 and 3 trials are awaited. [1] [55]

Researchers are also currently studying vaccines for ovarian cancer treatment, attempting to activate the immune cells to destroy the cancer cells. In ongoing ovarian cancer vaccine research, the potential tumor-associated antigen molecules targeted in ovarian cancer include CA-125, p53 protein, and HER-2. [55]  in one case study, vaccine therapy was used to amplify T-cell defensive responses. [56]  However, vaccine monotherapy has not been effective; therefore, most current ongoing pilot and phase 1 or 2 trials are investigating therapeutic vaccines in combination with other agents for ovarian cancer treatment. Other emerging therapies being studied in clinical trials are adoptive T-cell transfer and chimeric antigen receptor therapy as part of future strategies to ensure reduced cancer burden and improved life expectancy in this patient population. [1] [55]

Recurrent Ovarian Cancer

About 80% of women with advanced-stage ovarian cancer more commonly have tumor progression or recurrence. Platinum-free interval is one of the most reliable predictors indicating the response of recurrent ovarian cancer to subsequent chemotherapy. The platinum-free interval is the interval between the completion of the last platinum-based chemotherapy and relapse. [57]  However, platinum sensitivity generally refers to an interval of more than 6 months between the previous platinum-based chemotherapy cycle and the commencement of subsequent platinum-based chemotherapy. The role of surgery in cases of recurrent ovarian cancer is undefined. GOG-213, a phase 3 multicenter randomized clinical trial enrolled patients with platinum-sensitive recurrent ovarian cancer, randomized patients to surgical cytoreductive surgery followed by adjuvant platinum-based chemotherapy or only platinum-based chemotherapy with a primary endpoint of overall survival showed no improved benefit in patients receiving secondary surgical cytoreduction followed by chemotherapy and chemotherapy alone (hazard ratio for death 1.29, 0.97 to 1.72;  P  = .08). [58]  

The Desktop 3 trial, which compares surgery followed by chemotherapy versus chemotherapy only in recurrent platinum-sensitive ovarian cancer, is currently ongoing, and its results are eagerly awaited. Preliminary results showed improvement in progression-free survival and longer intervals to the start of subsequent chemotherapy in favor of surgery followed by chemotherapy. Additionally, 2 other trials, Surgery for Ovarian Cancer Recurrence (SOCceR) and Surgery or Chemotherapy in Recurrent Ovarian Cancer (SOC 1), are comparing surgery and chemotherapy with surgery alone in such groups of patients; the results are still awaited. However, current evidence has not shown longer overall survival with second-degree surgical cytoreduction in patients with platinum-sensitive recurrent epithelial ovarian cancer diagnosed surgery. [59]  

Large phase 3 trials have also resulted in the approval of bevacizumab, which was studied in combination with chemotherapy for the treatment of recurrent ovarian cancer as well as for maintenance therapy (GOG-218, or OCEANS and AURELIA trials). [57]  The studies have shown an objective improvement in progression-free survival. However, they failed to prove a benefit in overall survival. Nevertheless, anti-angiogenic agents have shown activity in these platinum-sensitive recurrent ovarian cancers, though further studies are needed to define their benefits clearly. Evidence shows the use of aromatase inhibitors like letrozole for the treatment of recurrent low-grade serous and endometrioid epithelial ovarian cancer based on large retrospective cohort studies.

PARP inhibitors have been under clinical development at various stages and have shown their efficacy in patients with germline  BRCA  mutations. They were first approved as monotherapy in ovarian cancer patients with deleterious germline or somatic  BRCA  mutations who have not responded to chemotherapy. Further studies showed significant progression-free survival benefits in patients with an initial response to bevacizumab with maintenance PARP inhibitor therapy. An overall survival benefit is yet to be proven, which requires a longer follow-up. SOLO-2 study assessed maintenance monotherapy with olaparib in patients with platinum-sensitive recurrent ovarian cancer and  BRCA  mutation, showing significantly improved progression-free survival for the patients receiving olaparib with no significant detrimental effect on the patient's quality of life. [60]  

PAOLA-1, a phase 3 trial, studied olaparib with bevacizumab in platinum-sensitive recurrent ovarian cancer, showing progression-free survival benefits in the patients receiving the combination. The results were consistent with those observed in the SOLO-1 trial. The safety profile of olaparib was relatively consistent in the trials, with a higher incidence of serious adverse events noted in the group receiving a combination of olaparib and bevacizumab than with placebo plus bevacizumab, the most common being anemia. [52]  Many phase 3 trials have shown PARP inhibitor maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer to have clinical benefits. However, study results also revealed that in patients who had HRD-positive advanced recurrent ovarian cancer treated with 3 (or more) prior chemotherapy regimens, PARP inhibitors could have detrimental effects. Therefore, olaparib, niraparib, and rucaparib are no longer recommended in the US for these patients. [46]

Platinum resistance confers an inferior prognosis, where these patients have a recurrence of the disease within 6 months of completion of cytoreductive surgery and adjuvant chemotherapy. Therefore, discussing care goals with these patients is imperative, as their overall survival rates are grim. Focusing on newer targets like tumor vasculature, DNA repair, intracellular signaling inhibition, and other molecular targets may provide more avenues to be explored for optimizing the treatment of recurrent ovarian cancer.

Consequently, those with advanced-stage ovarian cancer are generally treated with primary reductive surgery, followed by platinum-based chemotherapy. However, poor surgical candidates or patients who might not achieve effective cytoreductive surgery are recommended to undergo neoadjuvant chemotherapy. Optimal cytoreductive surgery is critical as reduced tumor burden is a powerful predictor of survival. Targeted therapies are the new emerging treatment strategies where bevacizumab and PARP inhibitors have become first-line therapies for maintenance, and PARP inhibitors are preferred for recurrent cases.

Ancillary Treatments

In addition to primary treatment for ovarian cancer, patients frequently will have ancillary considerations that require treatment. Induced surgical menopause secondary to bilateral salpingo-oophrectomy to treat epithelial ovarian cancers in those who are premenopausal may often necessitate treatment for vasomotor symptoms. In most of these patients, estrogen hormone therapy may be utilized according to ASCO, except in cases of low-grade serous and endometrioid ovarian cancers, as these histologic subtypes may be treated with antiestrogen therapies. [7]  Vulvovaginal atrophy and dyspareunia due to induced menopause or posttreatment complications may also require treatment. See StatPearls' companion reference, " Postmenopausal Syndrome ," for more information. Furthermore, contraception may be a consideration during treatment in patients who are premenopausal who have fertility-sparing surgery. The World Health Organization considers most contraceptive options safe, with only intrauterine devices having restricted use. [63]

Surveillance

Following primary ovarian cancer treatment, continued monitoring for any evidence of recurrence is necessary, though the precise duration and frequency have not been universally established. The NCCN guidelines recommend follow-up visits with a pelvic exam every 2 to 4 months for 2 years, then every 3 to 6 months for 3 years. After the first 5 years, follow-up can be performed annually. Furthermore, a CA-125 level should be assessed in patients with elevated levels before treatment. A complete blood count, comprehensive metabolic profile, and imaging should be performed when clinically indicated. [64]  Imaging modalities include chest, abdominal, and pelvic MRI, computed tomography (CT), or positron emission tomography (PET)/CT scan. NCCN guidelines also recommend that a genetic testing referral be offered if it has not already been done. However, some experts recommend routinely imaging and assessing a CA-125 level in patients with stage II to IV ovarian cancers every 3 months the first year, every 4 months the second year, every 6 months in years 3 to 5, and then every year thereafter, instead of just as clinically indicated. Monitoring bone mineral density in patients receiving an aromatase inhibitor is also recommended. [64] [65]

• Differential Diagnosis

The differential diagnosis for ovarian cancer includes:

• Colon cancer
• Embryologic remnants
• Gastric adenocarcinoma
• Metastatic gastrointestinal carcinoma
• Ovarian torsion
• Peritoneal cyst
• Retroperitoneal mass
• Uterine fibroids
• Papillary adenocarcinoma
• Serous adenocarcinomas
• Undifferentiated adenocarcinomas
• Small-cell adenocarcinomas
• Brenner tumors
• Radiation Oncology

Historically, whole abdomen radiation was used in an attempt to treat ovarian cancer; however, due to ineffective results and increased frequency of toxicity and complications, this modality is no longer used for this indication. Currently, the role of radiation in ovarian cancer is limited to palliation, either for symptom control or to treat a localized spread of the disease. Adjuvant radiotherapy has not shown any survival benefit in the early stages of clear cell carcinoma and high-risk disease, as ovarian cancer typically does not remain confined to the pelvis. [61] [62]

Due to the advent of advanced systemic therapies, radiation has taken a backseat in the management of ovarian cancer, offering limited use. Stereotactic body radiotherapy (SBRT) is a newer technique for palliative radiation. High rates of distant lesion progression still occur despite SBRT administration, even when local control is achieved. [62]  Currently, with the emergence of new techniques like SBRT, intensity-modulated radiotherapy, and low-dose hypofractionation, the role of radiation is being reconsidered for local-regionally recurrent ovarian cancer, especially for chemotherapy-resistant lesions. [63] [64]

• Medical Oncology

In patients with advanced disease or early-stage ovarian cancer with high-risk features (ie, stage IC and II, clear-cell histology, or high grade), chemotherapy following surgical cytoreduction is the standard treatment approach. Chemotherapy can be administered via intravenous (IV) or intraperitoneal routes, and several regimens are used, including platinum-based IV chemotherapy, platinum-based IV and intraperitoneal chemotherapy, and platinum-based intraperitoneal chemotherapy plus bevacizumab, depending on tumor histology, stage, and if optimal debulking was performed. [6]

In advanced-stage ovarian cancer cases, intraperitoneal carboplatin chemotherapy is well-tolerated. Since ovarian cancer growth is initially mainly in the abdominal cavity, intraperitoneal chemotherapy was thought to provide an increased therapeutic benefit by directly diffusing chemotherapeutic agents into cancer tissue, primarily for minimal amounts of remnant disease. Improved survival benefit of intraperitoneal chemotherapy was shown in 4 landmark trials: GOG-104, GOG-114, and GOG-172. However, the GOG-252 trial showed when bevacizumab was combined with intraperitoneal chemotherapy, adverse effects (eg, neutropenia, thrombocytopenia, neurotoxicity, and gastrointestinal symptoms) were increased, without any benefit in survival. Therefore, with the recent increase in the number of indications for bevacizumab, intraperitoneal chemotherapy is less utilized. [6] [65]  Additional trials are still underway, which may provide additional information on this treatment avenue. [6] [66] [67]

A phase 3 trial, GOG-111, showed improved overall survival in patients with a combination of cisplatin and paclitaxel when compared to the cohort receiving cisplatin and cyclophosphamide combination. The first line chemotherapeutic agent for epithelial ovarian cancer is platinum-based cisplatin or carboplatin, along with a taxane family agent, paclitaxel or docetaxel. Many study results have concluded that carboplatin is as effective as cisplatin and better tolerated. Additionally, weekly dose-dense chemotherapy with carboplatin and paclitaxel combination has not shown any additional benefit in progression-free survival than standard 3-weekly chemotherapy or an additional third agent or a longer period of the chemotherapy cycle. [6] [58]  Various effective chemotherapy regimens can be used. [22]  (see  Table.  Chemotherapy Regimen Options)  [22] [58]

Table. Chemotherapy Regimen Options.

  Chemotherapy in Older Adults

Patients 70 years and older with comorbidities who have stage III or IV ovarian cancer were studied in a randomized control trial, which showed worse survival outcomes with carboplatin monotherapy versus carboplatin-paclitaxel 3 weeks/weekly. [58]  But when combination therapy is being used, a modified dose-dense regimen of weekly carboplatin plus paclitaxel is better tolerated with a lower toxicity profile than the conventional dosing (3 weeks schedule) in these patients. However, progression-free survival was not prolonged, as shown in an MIT07 phase 3 trial, which can also be used for older patients with comorbidities. [68] [69]  Older adults with frailty were found to have decreased high-grade neutropenia, febrile neutropenia, thrombocytopenia, and neuropathy. [21] [58] [70]

Ovarian cancer is surgically staged according to the 8th edition American Joint Committee of Cancer (AJCC), International Federation of Gynecology and Obstetrics (FIGO) staging system, and corresponding TNM classification. [21]  (see  Table . International Federation of Gynecology and Obstetrics Ovarian, Fallopian Tube, and Peritoneal Cancer Staging System). When the primary site can be determined (ie, ovary, fallopian tube, or peritoneum), the designation should be noted; tumors where the primary site can not be differentiated should be documented as “undesignated.” [21]

Table. International Federation of Gynecology and Obstetrics Ovarian, Fallopian Tube, and Peritoneal Cancer Staging System.

Ovarian cancer has a generally poor prognosis, with a 5-year survival rate of less than 50% and a 10-year survival rate of approximately 35%. [71]  The prognosis of ovarian cancer is directly dependent on the disease stage at the time of diagnosis. The survival rate for stage I ovarian cancer is estimated to be between 70% to 92% compared to less than 6% for stage IV tumors. [72]  Other factors associated with prognosis include baseline performance status, histologic type and grade, and volume of residual disease post-primary cytoreductive surgery. Because the amount of residual disease after primary debulking surgery impacts prognosis so significantly, guidelines recommend that this treatment should be performed in any patient able to tolerate surgery. [21]

In women with a disease that has spread to adjacent tissues, 5-year survival rates drop down to 80% and 25% for the ones with metastatic disease. [73]  Select patients with recurrent disease can sometimes be treated with secondary cytoreductive surgery. Factors associated with better surgical outcomes in patients with recurrent ovarian cancer include a contained tumor recurrence site and ascites less than 500 mL. Prognosis is also better in patients with recurrent platinum-sensitive ovarian cancer compared to platinum-resistant recurrent tumors, which typically are only given palliative therapy. [37] [72] [74]

• Complications

Women who could not be offered treatment frequently have severe complications like ascites, bowel obstruction, pleural effusion, and bladder obstruction, apart from disorders of nutrition. [75]  Women who succumb to ovarian cancer frequently have various complications in the last 6 months of life, including:

• Fatigue or weakness
• Nausea or vomiting
• Constipation
• Pedal edema
• Anemia  [75]

Complications that may develop following ovarian cancer treatment include depression, anxiety, neuropathy, pelvic pain, fatigue, nausea, decreased libido, dyspareunia, and vaginal dryness. Reduced quality of life is also common due to secondary effects on a patient's ability to work and finances. [7]  General adverse effects secondary to chemotherapy include catheter complications, nausea, vomiting, dehydration, and abdominal pain. [76]

The adverse effects of bevacizumab, the anti-angiogenic inhibitor, include headache, epistaxis, hypertension, proteinuria, rhinitis, altered taste, dry skin, exfoliative dermatitis, rectal hemorrhage, and abnormal lacrimation. The most severe adverse effects include gastrointestinal perforation, impaired wound healing, and hemorrhage, which are included as black-box warnings. Clinicians should inform patients of these complications and instruct them on symptoms that require evaluation. [77]

• Consultations

Determining the risk of malignancy solely based on clinical features is often inaccurate. Therefore, most professional societies, including the NCCN and the American College of Obstetricians and Gynecologists (ACOG), recommend referring all patients with suspected ovarian malignancies to a gynecologic oncologist for further evaluation and treatment because of significantly improved survival. [7]  ACOG also provides specific guidance, stating that for patients with an adnexal mass and any of the following findings, clinicians should consult a gynecologic oncologist: 

• Ultrasound findings of ascites, a nodular or fixed pelvic mass, evidence of abdominal or distant metastasis, or other features suggestive of malignancy
• An elevated CA-125 level in those who are postmenopausal 
• A significantly elevated CA-125 level in those who are premenopausal 
• An elevated score on a formal risk assessment test (eg, the multivariate index assay, risk of malignancy index, or the risk of ovarian malignancy algorithm) or an imaging-based scoring system  [7]
• Deterrence and Patient Education

At the time of diagnosis, the patient should be counseled on their prognosis and all available treatment options. Genetic counselors and oncology clinicians should counsel all patients with ovarian cancer regarding genetic testing, especially for patients with hereditary cancer syndromes. [6]  The palliative care team and other related consultants should be promptly involved regardless of cancer stage to enable comprehensive care, anticipate the disease course, and significantly impact the patient's quality of life. Patients should also be advised on ongoing clinical trials if pertinent to their particular case.

Furthermore, results from several studies have demonstrated that increased physical activity is associated with a decreased risk of ovarian cancer. [15]  Obesity and diabetes are also established risk factors for ovarian cancer. Because of this association, some recent studies have proposed that preventative interventions for these conditions may impact the development of ovarian cancer. [71]  ACOG also recommends bilateral salpingo-oophorectomy at 35 to 40 years for those carrying  BRCA1  mutations and by age 40 to 45 in women with  BRCA2  mutations to reduce ovarian cancer risk. In women of average risk for ovarian cancer, salpingectomy at the time of hysterectomy or as a sterilization method is appropriate as a means for ovarian cancer risk reduction. [7]  

• Enhancing Healthcare Team Outcomes

Ovarian cancer, despite ongoing clinical trials and advancements in treatment, remains a significant challenge in women's health due to late-stage diagnosis and deviation from recommended care guidelines. Efforts are needed to develop effective strategies for early detection and optimize treatment outcomes. Experienced gynecologic oncologists are critical in achieving optimal cytoreduction surgery, a key determinant of patient survival. Interprofessional collaboration, particularly between medical and surgical oncologists, facilitates shared decision-making regarding treatment options and enrollment in clinical trials. Pathologists provide essential diagnostic information through tissue biopsies, guiding treatment decisions. Early involvement in palliative care improves treatment efficacy and enhances patients' quality of life. Close surveillance and patient education on symptom recognition for disease recurrence are vital for long-term management. With its complex nature and diverse treatment modalities, ovarian cancer care necessitates a patient-centered approach, integrating the expertise of physicians, advanced practitioners, nurses, pharmacists, and other health professionals to improve patient outcomes, safety, and team performance.

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Disclosure: Taruna Arora declares no relevant financial relationships with ineligible companies.

Disclosure: Sanjana Mullangi declares no relevant financial relationships with ineligible companies.

Disclosure: Elsa Vadakekut declares no relevant financial relationships with ineligible companies.

Disclosure: Manidhar Reddy Lekkala declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Arora T, Mullangi S, Vadakekut ES, et al. Epithelial Ovarian Cancer. [Updated 2024 May 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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