September is Ovarian Cancer Awareness Month/Gynecologic Cancer Awareness Month. Gynecologic Oncologist Angeles Secord, MD, MHSc, shares insight on ovarian cancer in this Duke Cancer Institute article, and is committed to conducting innovative research with nationally renowned colleagues to provide options for cancer patients through clinical trials and ongoing studies.
Dr. Secord advises that while these cancers frequently cause non-specific symptoms that can be hard to identify, women should seek prompt medical attention if any of these common symptoms (bloating; pelvic and/or abdominal pain; feeling full quickly, upset stomach, or trouble eating; having to urinate frequently; extreme tiredness; difficulty having bowel movements; and abdominal swelling) last more than a few weeks.
Clinical Trials and Advancements in Care
At the 2020 IGCS2020 virtual meeting, Dr. Secord's work (along with colleagues from leading cancer institutes and universities through the nation) on a promising clinical trial for cancer patients will be presented at the plenary presentation on Sept. 13, 2020: Quality-adjusted (QA) progression-free survival analyses of veliparib + carboplatin/paclitaxel (CP) vs CP alone in patients with newly diagnosed ovarian cancer.
"Our findings showed that the addition of veliparib to chemotherapy and continued as maintenance had significant patient-centered benefits in terms of quality adjusted-progression-free survival and Q-TWiST analyses (time without symptoms of disease or treatment toxicity)," noted Dr. Secord.
Complete study summary: While poly (ADP-ribose) polymerase (PARP) inhibitors have been shown to improve progression-free toxicity, they are associated with toxicity and increased cost. In order to better understand the benefit of therapy and trade-offs, we conducted quality-adjusted progression-free survival and TWiST (time without symptoms of disease or treatment toxicity) analyses in patients with newly diagnosed stage III/IV high-grade serous epithelial ovarian/fallopian tube/primary peritoneal cancer who participated on the Phase 3 VELIA trial (NCT02470585). The VELIA trial evaluated veliparib, a PARP inhibitor among VELIA patients who were randomized to veliparib added to standard chemotherapy followed by veliparib maintenance compared to those treated with standard chemotherapy and placebo followed by placebo maintenance. The VELIA study was unique from most PARP inhibitor studies, because the PARP inhibitor was given with chemotherapy and for maintenance and not just maintenance alone. The addition of PARP inhibitor with chemotherapy may increase toxicity further. Our findings showed that the addition of veliparib to chemotherapy and continued as maintenance had significant patient-centered benefits in terms of quality adjusted-progression-free survival and Q-TWiST analyses.
Continuous Support Needed
An annual tradition for helping to raise funds for research such as this is the annual Gail Parkins Ovarian Cancer Walk & 5K Run. The event, in its 18th year, will be virtual this year and takes place Sept. 12 through Sept. 26th. The more than $4 million raised since the first event has helped fund several Duke studies — from the impact of ovarian cancer treatment on quality of life to investigations into the impact of genetic alterations on disease progression and implications for new therapies.
Read more about Emerging Options for Gynecologic Cancers here.
More about the Gail Parkins Ovarian Cancer Walk & 5K Run
Menopause and Midlife Management Tips — and Workign Toward Positive Goals
Dr. Camille Moreno is a North American Menopause Society Certified Menopause Practitioner (NCMP). Her clinical practice is dedicated to an interdisciplinary women’s health practice focusing on:
- The care of midlife women as it relates to menopause, perimenopause and hormone therapy
- Surgical or radiation-induced menopause
- Use of bioidentical hormone therapy
- Midlife weight management
New Year's resolutions are on our minds in January, and often include aspirations that may cause stress and feelings of inadequacy if not accomplished. My goal is to help women achieve their optimal health by inspiring and involving them to be their own health advocates. I want to be able to constantly remind and inform them of their goals as well as provide them with my expertise and resources to achieve them. Health-related concerns beyond the childbearing years are often dismissed and ignored. This is why a significant part of my career is dedicated to an interdisciplinary women’s health practice focusing on the care of midlife women as it relates to menopause, perimenopause, hormone therapy and their associated medical problems.
Whether you're just entering menopause or you have been dealing with bothersome menopausal and perimenopausal symptoms for months, you are not alone. Be confident that you have several treatment options available. The tips below offer ways to proactively manage your health.
1. Schedule your yearly health visit. Even if you are over 65 years of age and no longer need Pap and HPV testing, you should not skip your yearly health maintenance visit. This is the time for you to discuss with your medical provider any symptoms you may have from hormonal fluctuations or lack of estrogen.
2. Move more and sit less. Exercise has been shown to decrease the frequency and intensity of hot flashes and improve mood swings during the menopausal transition.
3. Eat more plants (90-95% of intake should be vegetables, grains, greens, fruits and beans). Eat whole foods or foods processed with less than 5 ingredients. Primarily drink water. Decrease sugar consumption and consume only 28 grams or less of added sugar daily.
4. For women with low libido or clinically diagnosed Hypoactive Sexual Desire Disorder, there are new therapies available, including Vyleesi®/Bremelananotide, a new on-demand injectable therapy.
5. For postmenopausal women desiring bio-identical therapy, there is a new menopausal hormonal formulation treatment: Bijuva® (estradiol/progesterone in coconut oil).
6. For women who need a medication with bone-building (anabolic) properties and anti-resorptive effects, there is a new bone-building monthly injectable (12-month): Evenity®/Romosozumaub.
Appointments: Visit dukehealth.org to learn more and make an appointment with Dr. Moreno and other Duke Ob/Gyn Providers.
Megan Huchko, MD, Associate Professor of Obstetrics & Gynecology, describes her experience and motivation that led her to a career as an implementation scientist, what led her to conduct research in East Africa and the effectiveness of cervical cancer prevention.
How did you originally get interested in global health?
I have always been interested in traveling, and in college, had the opportunity to study abroad in Madrid, Spain. While I was there, I was immediately struck by the entrenched gender roles and overt masculinity that seemed to permeate both professional and personal spheres. Every day on the way to class, I would pass by the Institute of the Woman, which was a government agency created by the relatively recent constitution to ensure equality between the sexes. I developed that curiosity into a research project on the women’s movement in Spain that I was able to carry out through a Fulbright Award after I graduated. During my Fulbright year in Spain, as I was interviewing activists and feminists in Spain about political and social advances for women over the previous two decades, there were several egregious instances of domestic violence that inspired something of a national soul-searching. I decided to use the legal and social climate around domestic violence as a case-study to illustrate the limitations of the women’s movement and the absolute centrality of health and safety from violence to a person’s well-being. While this case-study was not uniquely “global health,” the experience jumpstarted my interest in the political, social and cultural drivers of health, which are often seen most acutely in global health.
Why have you focused your work in East Africa?
During my fellowship in Reproductive Infectious Disease, I started working at the Family AIDS Care and Education (FACES) program in western Kenya. My mentor had started FACES through a US government funding program called PEPFAR, which provided funding for HIV care for the hardest hit countries in the world, the majority of which are in sub-Saharan Africa. In addition to having an incredibly high HIV-prevalence, this region had poor maternal health outcomes and poor access to reproductive health care. At the same time, Nairobi is one of the most cosmopolitan cities in Africa, with an increasing number of people interested in public health research. I was able to capitalize on my mentor’s infrastructure and relationships as I established my own research program. When I came back to Duke a few years ago, I found that the Global Health Institute had strong relationships in Kenya, Tanzania and Uganda, so it made sense to develop a Center for Global Reproductive Health with a focus area in East Africa.
Can you describe the type of research that you do?
I am an implementation scientist, which means that I work on strategies to bridge the gap between evidence-based interventions and the populations they are targeting. Specifically, I have worked to develop implementation strategies for cervical cancer prevention for women in low-resource settings, mainly in East Africa. The focus of the work has evolved as the technology and funding for cancer prevention has advanced. In my early career, I worked to help develop evidence for various screening strategies in different populations and settings. At this point, my main focus is on working with guidelines committees to develop strategies for specific populations, and working with key stakeholders to identify ways to successfully implement these strategies.
What are some of the most exciting advances in cervical cancer prevention in the past few years?
Progress in cervical cancer prevention has driven the WHO to issue a Global Call for Elimination within the next 100 years. Although this is an ambitious target, it has lead to increased funding to spark creativity in the development and implementation for the latest tools and strategies to deliver primary and secondary prevention. Clearly the biggest impact has come from the introduction of the HPV vaccine almost 20 years ago, now available in a formulation that provides protection against up to 96% of cervical cancer. This aligns with further developments in HPV testing, both in molecular genotyping and in advances that make this technology more feasible in low-income settings (evidence for self-collection and lower cost, more durable testing platforms). One of the most exciting recent advances is the development of visual algorithms for the diagnosis of cervical cancer precursors, which some are calling artificial intelligence. If successful, they could increase the accuracy of cervical assessments over HPV testing alone, in areas where coloposcopy and pathology are not available. This would decrease the burden of overtreatment on the individual woman and on the health care system. The technological advances in screening and vaccination leave remaining challenges in devising implementation strategies that will meet the needs of the populations most in need.
How can lessons learned in East Africa translate to effective cervical cancer prevention in the US?
We live in a state with marked disparities in cancer rates between urban and rural populations. Working in the cervix clinic, I can see firsthand the burden that some patients have to get to the 1J; they have to drive hours from their home, and then navigate a somewhat complex medical system. Some of the engagement and follow-up strategies we are working on in Kenya and East Africa may help address attendance: mHealth education and reminders. More ambitiously, I was part of a multidisciplinary group that included the Pratt School of Engineering and the Margolis Center to develop and evaluate new models of decentralized care across the screening, diagnosis and treatment cascade. While there are unique challenges and assets in the US, many of the strategies we described derived from our work in East Africa.
How have students or residents been involved with your work?
I’ve had students and residents work on various aspects of the cervical cancer prevention and health systems strengthening work, both through on-site rotations and through data analysis in the US. The Center for Global Reproductive Health has a network of researchers in East Africa who are working on various projects, from HIV care and prevention, women’s mental health, safe motherhood, and big data analytics around family planning – we are always happy to work with learners to see if there is a fit for research interests, or ways we can work together to develop new ideas.
Nov. 14, 2019 recognizes Genetic Counselor Awareness Day, sponsored by the National Society of Genetic Counselors. Genetic Counselor Awareness Day is dedicated to raising awareness and utilization of genetic counselors in communities and institutions. It is also our goal to help consumers understand the importance of the supportive roles of genetic counselors in health care.
Genetic counselors are healthcare professionals with advanced training in medical genetics and psychosocial counseling who partner with patients seeking information about inherited conditions affecting them or their families. Genetic counselors work with patients and their physicians to understand family history, discuss the risks, benefits and limitations of genetic testing, interpret results and implications of genetic testing, and help communicate this information to family members.
Over 5,000 certified genetic counselors (CGC) practice in a variety of healthcare settings in the United States, including but not limited to prenatal, fertility, pediatrics, metabolic, cardiovascular, neurology, and cancer care. Genetic testing has become an integral part of patient care, and partnering with genetic counselors has never been more important than now.
Genetic Counselor Awareness Day is a great opportunity to highlight the value of the genetic counselors in our Department in promoting patient care and ensuring that physicians and patients have access to genetic counseling and testing at our institution.
The Department of Ob/Gyn, together with the Department of Women and Children’s Services, are fortunate to have six certified genetic counselors who see patients in one of five clinical locations: Fetal Diagnostic Center, Duke Perinatal Durham, Duke Perinatal Burlington (at Alamance Regional), Duke Perinatal Cary and Duke Perinatal Raleigh. We welcome the opportunity to assist you with your patients and to be available to you as questions arise. Please join us in celebrating our Department’s accomplished Genetic Counselors:
Michelle Baric Humphries, MS, CGC: 6 years of clinical practice. Specializes in prenatal and preconception genetics. Sees patients at Fetal Diagnostic Center and provides additional coverage to Alamance Regional.
Regan Challinor Matthews, MS, CGC: 21 years of experience. 6 years of clinical practice. Specializes in prenatal and preconception genetics. Sees patients at Fetal Diagnostic Center.
Kristin Paulyson Nuñez, MS, CGC: 25 years of experience. Specializes in preconception and prenatal, blood disorders and teratology. 2020 President-Elect of American Board of Genetic Counseling. Sees patients at Fetal Diagnostic Center, Duke Perinatal Durham and provides additional coverage to Alamance Regional.
Amanda Padro, MS, CGC: 12 years of experience. Specializes in preconception and prenatal. Sees patients at Duke Perinatal Raleigh and Duke Perinatal Cary
Patricia “Trish” Thompson, MS, CGC: 6 months of experience. Specializes in preconception and prenatal. Sees patients at Duke Perinatal Cary and Duke Perinatal Raleigh.
Deborah Franks Wells, MS, CGC: 22 years of clinic experience. Provides counseling at Duke Perinatal Burlington for prenatal and preconception indications.
Jennifer Gilner, MD, PhD , Assistant Professor of Obstetrics & Gynecology, describes the experiences and motivations that led her to a career as a physician-scientist in high risk obstetrics, and current challenges she is leveraging Departmental and SOM resources to address.
Describe your path to becoming a physician-scientist in obstetrics.
I enjoy science that explains the causes and connected steps leading to disease presentation in medicine. The combined MD/PhD training track fit my method of learning medicine through science and mechanism, and inspired me to think that I could practice medicine and find ways to advance medical treatments by learning from my patients. I started out in research studying the highly ordered blood clotting cascade and the system of blood cell formation, called hematopoiesis. I earned my PhD in Pathology, the study of mechanisms of disease, working with physician-scientists specialized in hematology/oncology and hematopoietic stem cell transplantation. This work exposed me to the amazing complexities of immune system reactivity versus tolerance in transplantation, the fascinating biology of human development, and eventually connected me to Dr. Joanne Kurtzberg and the Carolinas Cord Blood Bank, since cord blood has special properties that make it an ideal source of hematopoietic stem cells.
Clinically, I was captivated by obstetrics in my very first clinical rotation of medical training. The fast pace, need for quick decisions, and combination of in-depth medical understanding with frequent hands-on procedures made Maternal-Fetal Medicine a clear choice for me. Obstetrics is not the most common path for MD/PhD trainees, but there are many opportunities for advancing the basic science understanding of pregnancy disorders, so I felt I could make a contribution while practicing the field of medicine that fits my personality and interests.
How you were drawn into preterm birth research?
The path to preterm birth research for me was paved in part by personal experience and in part by responding to the gaps in effective treatments I have been able to offer my patients. My first child was born prematurely, after my water broke early. She was born before I had completed medical training – in fact before I had even identified obstetrics as a specialty I would consider – so I lived through that experience as a patient without prior experience or frame of reference for my situation, much like the majority of patients I care for today. Ultimately, my daughter and I were lucky to have an overall smooth course without long-term sequelae, but the experience gave me the first-hand patient viewpoint that helps inform my counseling and discussion with my obstetric patients. As that personal experience sparked my curiosity, (and gave me understandable anticipatory anxiety in subsequent pregnancies) I took advantage of my medical training and learned that preterm birth, or delivery of a pregnancy prior to 37 weeks of gestation, affects about 1 in 10 pregnancies. Unfortunately, the rate in the United States has been incrementally increasing for the past few years. Most women who deliver preterm do not have known or identified risk factors before the preterm delivery event, and the majority of preterm births do not have a specifically identified cause.
Furthermore, our treatment options remain limited, as even the most effective interventions we have only work for about a third of the women we prescribe them to. I hope to use my background and training to move this bar, and eliminate some of the helpless feelings I share with the patients that are affected by preterm birth and its long-term sequelae for both moms and babies. How does your approach to preterm birth research differ from commonly published or historical approaches? Obstetricians have traditionally used only broad clinical characteristics, such as spontaneous labor and delivery versus medically-indicated delivery caused by issues like preeclampsia, to group different types of preterm birth for research purposes and for deciding which treatments to try for prevention. In grouping patients this way, the field has certainly made some important advances, but the screening and treatments we have to offer currently, such as cervix length ultrasound to identify vaginal progesterone candidates, or use of cervical cerclage, only seem to work for a fraction of the patients we identify as eligible.
Despite these advances, our rate of preterm birth is still gradually climbing. There is good evidence that risk factors overlap between these clinically defined categories; that is, if a woman has a history of preeclampsia, her future pregnancy has elevated risk for spontaneous preterm birth as well as recurrent preeclampsia. Taken together, this means it is time for obstetric scientists like me to think outside of these traditional clinically-defined groupings and to find better ways to identify the underlying disease mechanism in each patient case.
There are several proposed disease mechanisms that result in preterm birth, such as infection seeded by pathogens ascending from the vagina, immune system disruption, or cervical weakness – but the critical factor we are missing is the ability to pinpoint which of these disease processes is happening in an individual patient. I endorse the approach of seeing preterm birth as a common endpoint for many different individual disease states, so the primary objective is to uncover ways to clearly identify mechanism-based characteristics in these women so that our prevention and treatment strategies can be better tailored to the underlying cause of her pregnancy disorder. I have committed my research to better understanding the disease mechanism of immune tolerance in pregnancy, and identifying the ways in which maternal immune tolerance is disrupted in women who deliver preterm. What have been the main barriers to this approach to date? Immunology of pregnancy is not a new field, but our depth of knowledge is poised to explode with the recent advances in high-throughput methods to study immune cells. The concept of an immunologic ‘mismatch’ between mom and fetus was introduced by a famous immunologist and Nobel Laureate named Peter Medawar in the 1950s. Dr. Medawar’s original proposals of how the maternal immune system can accept the fetus during pregnancy have turned out to be incorrect, but he is credited with ‘opening the conversation.’ Much of the foundational work on the specialized immune mechanisms in pregnancy have been done by reproductive immunologists trying to understand what causes recurrent pregnancy loss or prevents establishment of a pregnancy. The fundamental challenge to continuing this type of work into later timepoints in pregnancy (such as the gestational weeks when preterm birth occurs) is getting access to that maternal-fetal interface. For obvious reasons, we cannot biopsy a placenta or uterine lining mid-pregnancy. We rely on animal models to some degree – but the structure of the placenta is a bit different in humans, so the animal models just provide a starting point. In my lab, I have dedicated my time and research questions to learning how the peripheral circulating immune cells change in pregnancy, and to learning how to harvest and investigate the immune cells that are adherent to the placenta at delivery.
I have built a repository of patient-donated placenta and blood samples from over 200 preterm deliveries, which gives me the opportunity to characterize maternal T cell function over a wide variety of preterm birth disease states. What will it take to advance the field of immune tolerance in preterm birth? Collaborative research and biobank resources. I am thrilled to be at Duke, where the Institutional, School of Medicine, and OB/Gyn Departmental leadership understand the need for multidisciplinary science and have aligned resources accordingly. Technology for studying immunology and cellular biology has advanced leaps and bounds in the 12 years since I finished graduate school. The Translating Duke Health Immunology initiative has provided research funding and opportunities for collaboration that allow me to apply cutting edge techniques to answer pregnancy-specific questions.
The diversity of preterm birth requires large patient cohorts to identify meaningful patterns of disease. As an affiliate faculty of the Translating Duke Health: Duke Children’s Health and Discovery Institute I can leverage the infrastructure of programs such as the HOPE1000 maternal and child biobank, and connect my findings to the work of researchers studying long-term effects of pregnancy events on childhood health.
Susan K. Murphy, PhD , Associate Professor of Obstetrics and Gynecology and Chief of the Division of Reproductive Sciences, describes how she became involved in this area of research and her most surprising discoveries to date.
What kind of research are you engaged in?
My research is focused on understanding the factors that predispose us to health and disease starting from before the beginning of life prior to conception, through gestation. At the other end of the spectrum, I also study ovarian cancer with a particular emphasis on trying to identify features of the disease that can be used to delay or even prevent recurrence. The common thread that integrates all of my research is the role of epigenetic modifications in changing gene expression.
What is epigenetics?
Epigenetics refers to mechanisms our cells use to help regulate the activity of genes throughout the genome. I study DNA methylation, which involves the addition of a methyl group (a carbon and three hydrogen atoms) to specific regions of the genome, which is a normal and essential process for normal cell function. The fidelity of the processes guiding addition and removal of methyl groups to the DNA is sensitive to nutrition (from where methyl groups are derived), hormone levels and other exogenous exposures like tobacco smoke or air pollution. These exposures can cause abnormal addition or removal of methyl groups, leading to altered gene expression and cell behavior, which can increase risk of disorders and disease.
How did you become interested in this research?
I first entered the field of epigenetics after the loss of my oldest son to hepatoblastoma when he was 3 years old, and this happened three months after a diagnosis of autism for my younger son at age 2. I was in my second year of graduate school at the time, studying to become a virologist. For me, these profound events made me rethink what I wanted to devote my career to. I decided to pursue my postdoctoral training learning epigenetics, since it is highly relevant to both neurodevelopmental disorders and cancer.
What is your most exciting or surprising finding?
There are two. The first was that there are drugs we identified using a bioinformatics approach that more effectively target slow growing cancer cells as compared to the majority of chemotherapeutic agents that target actively proliferating cells. We believe that recurrent ovarian cancer arises from cells that survive the initial chemotherapeutic treatment in part because they go into a slow-growing or dormant state, and that these cells will eventually begin to regrow to cause recurrence. These findings may lead to novel therapies that could be used to maintain a state of remission for women who, unlike many women with breast cancer, do not have any therapeutic options to prevent recurrent disease. The second is our recent finding that the use of cannabis leads to substantial changes in the DNA methylation profile in human sperm. We showed similar changes in rats exposed to tetrahydrocannabinol (THC, the major psychoactive component of cannabis). Most surprisingly, however, was that multiple genes in the same developmental and cancer-related biological pathways were affected by these changes in both rats and humans. We are currently working on a larger study to confirm our findings and to examine the potential for transmitting these changes in DNA methylation to the next generation.
What is the best advice you received that you like to pass on to young scientists?
First, find your passion and pursue it with everything you have. I love what I do and am lucky to have outstanding lab staff and trainees, all of whom share the same sense of wonder and curiosity with me and each other. Keep an open mind; have patience; network. Treat everyone with respect. There is no stupid question. Ask. Always do your best work with the highest level of care and integrity. Take responsibility. Own your mistakes and learn from them
Duke urogynecologists evaluate and treat women with the full spectrum of conditions related to the bladder and reproductive organs. Patients are seen by both urogynecologists and Advanced Practice Providers (APPs) to find the best treatment plans for patients. The team works together as a whole to provide a spectrum of care.
Learn more about our urogynecology APPs below!
Katelyn C. Smith, MSN, FNP-C
Nurse Practitioner – Obstetrics and Gynecology
Duke Urogynecology Consultants Navaho – Raleigh, NC
Cassandra Shaw, MSN, WHNP-BC
Nurse Practitioner – Obstetrics and Gynecology
Duke Urogynecology – Durham, NC
What areas do you specialize in?
Cassandra: I’m a nurse practitioner who specializes in improving the quality of life of women with pelvic floor disorders, including conditions like urinary incontinence, urinary tract infections and vaginal prolapse. These are common disorders, but they can be difficult and embarrassing to manage.
Katelyn: I’m a nurse practitioner who works with conditions such as urinary incontinence, painful intercourse, non-surgical management of vaginal prolapse and recurrent urinary tract infections. I specialize in helping women who struggle with these pelvic floor disorders return to normal life.
What is your philosophy toward patient care?
Katelyn: Pelvic floor disorders affect millions of women around the world, but I enjoy tailoring the treatment approach to individual patients and utilizing evidence-based medicine.
Cassandra: I like to customize my care to the patient’s unique situation and her own goals. Together, by collaborating with patients, we’re able to come up with a plan and help patients gain control of their lives and their health. It’s really empowering.
What are the benefits of being within the Duke Health System?
Cassandra: We’re able to connect patients to the resources they need. Duke Health is a very multidisciplinary system and it’s rewarding to be able to help patients find everything that they need within the Duke system.
Katelyn: At Duke, we are able to have the most advanced treatment options at our fingertips, and can stay up to date with new research.
What is the most rewarding or impactful part of your job?
Katelyn: I am pleased to see my patients enjoying life again once their symptoms are managed.
Cassandra: I love listening to my patients and having conversations with them about how they are affected by what they are experiencing, as well as the various treatment options.