By Mary Daly, MD, PhD, FACP
Chair, Department of Clinical Genetics, Fox Chase Cancer Center
Founder, Margaret Dyson Family Risk Assessment Program,
Fox Chase Cancer Center
Director, Ovarian Cancer Consortium for Research and Surveillance
There are several women in my family who have had breast cancer and ovarian cancer. How do I find out if I am at risk of developing ovarian cancer and whether I should have my ovaries removed prophylactically?
Most women who get ovarian cancer—90 percent in fact—have no known hereditary factors for developing the disease. The other 10 percent of diagnoses, however, are tied to hereditary factors, so being aware of your family history is certainly important.
We’ve learned that there are at least two hereditary cancer syndromes linked to genetic mutations. The most common are the breast cancer gene mutations, referred to as BRCA1 and BRCA2. While women in the general population have a 2 percent chance of developing ovarian cancer by age 70, women with the BRCA1 mutation have an approximate 40 percent chance, and those with BRCA2 have a 10 percent chance.
Equally as common are genes related to Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), which is associated with families in which members have had colon cancer, uterine cancer, or ovarian cancer at a young age. Women who inherit HNPCC-related genetic mutations have a 12 percent lifetime risk of ovarian cancer as well as increased risk of colon, stomach, and uterine cancers.
To fully understand your risk of ovarian cancer, it is important to conduct a formal risk assessment with a genetic counselor who is specially trained to provide information and advice about inherited conditions. The counseling should include analysis of your family tree, education about genetic-testing options, testing if appropriate, discussion of test results, and further counseling about risk-reducing options if you are found to be at high risk.
It is important to remember that even if you have a strong family history of ovarian cancer, you may test negative for the BRCA1/2 or Lynch syndrome mutations. If these mutations have been confirmed in your relative with ovarian cancer yet your test is negative, you did not inherit the gene that runs in your family and your risk is considered the same as that of women in the general population.
If these mutations have not been confirmed in your family, however, you are still considered to be at higher risk of developing ovarian cancer than women in general, based on your family history.
Genetic testing can be expensive—the cost for the first person in the family to be tested for BRCA1/2 or Lynch syndrome can exceed $3,000—but most insurance companies cover the cost if the criteria are met. If the first person tested in a family has a positive result, the rest of the family is tested just for that mutation, and the cost goes down to about $300 to $400.
If you are found to be at increased risk of ovarian cancer, your doctor may recommend prophylactic oophorectomy, or removal of the ovaries and the fallopian tubes. Expert organizations such as the National Cancer Institute traditionally recommend that high-risk women consider this surgery by age 35 or after childbearing is completed. They qualify this recommendation, however, by stressing that the decision should be made on a case-by-case basis.
Women consider this surgery because ovarian cancer is a serious disease that tends to be diagnosed at a later stage after it has spread beyond the ovaries, which makes it difficult to cure. Also, because the ovaries are located deep in the body, early-stage tumors are difficult to detect through physical examination or imaging. A third reason is because the blood test for the CA-125 protein is not always reliable.
Risk-reducing surgery has been proven in research studies to be effective in reducing the risk of ovarian cancer by 75 to 95 percent (primary peritoneal cancer remains a risk) and the risk of breast cancer by 50 percent. Women also find that surgery is a way to take control of an anxiety-producing situation.
Prophylactic oophorectomy is not without side effects, particularly for premenopausal women. For this reason some women opt not to have surgery or to delay it. For women who are premenopausal, the surgery can cause sudden rather than gradual symptoms of menopause, including hot flashes, vaginal dryness, and reduced libido. The absence of ovaries and the reduced estrogen may also cause such symptoms as insomnia, muscle pain, and mood swings as well as a long-term risk of osteoporosis and cardiovascular disease. Many of these symptoms can be addressed with exercise, medication, and other interventions. In the face of this choice, some premenopausal women choose a “wait and watch” strategy, with regular pelvic ultrasounds and CA-125 blood tests.
If you choose risk-reducing surgery, you may want to consider a gynecologic oncologist trained in surgery and oncology because occasionally women are found to have ovarian cancer at the time of the surgery, and the surgeon can convert the prophylactic surgery to a therapeutic surgery.
Decision-making about risk-reducing surgery is a complex process, and what feels right for one woman may not be right for another. Consult with family members, physicians, genetic counselors, and support organizations. Take the time you need to have your questions answered and become comfortable in your plan.
Ovarian Cancer Risk-Reducing Surgery: A Decision-Making Resource (Philadelphia: Fox Chase Cancer Center, 2006).
Mary Daly, MD, PhD, FACP, is chair of the Department of Clinical Genetics at Fox Chase Cancer Center in Philadelphia, where she holds the Timothy R. Talbot Jr. endowed chair in cancer research and has a joint appointment in the Medical Science Division. She focuses on women’s health and is the founder of the Margaret Dyson Family Risk Assessment Program, evaluating preventive approaches to breast and ovarian cancer. Her primary areas of research include the epidemiological and genetic aspects of breast and ovarian cancer and the translation of this information into effective cancer prevention. As director of the Ovarian Cancer Consortium for Research and Surveillance, she has initiated studies of ovarian cancer screening methods, quality of life after preventive surgery, and serum biomarkers of breast cancer risk. As principal investigator of the Cooperative Family Registry for Breast Cancer Studies, she is collaborating with institutions worldwide to study the patterns of familial breast and ovarian cancer, gene-environment interactions, and the development of novel, genetics-based therapeutic and preventive strategies. She has been recognized as a leader in the design of educational programs in cancer genetics and cancer risk for both high-risk individuals and their healthcare providers.
Decisions about cancer treatment and prevention can be difficult. With the advent of personalized medicine, many new resources are available to aid women in those decisions. Below is a list of organizations that offer a variety of information on genetic risk factors and ovarian cancer.
American Board of Genetic Counseling, www.abgc.net or (301) 571-1825
Association of Cancer Online Resources, www.acor.org
FORCE: Facing Our Risk of Cancer Empowered, www.facingourrisk.org or (866) 288-RISK
Margaret Dyson Family Risk Assessment Program at Fox Chase Cancer Center, www.fccc.edu/rap or (877) 627-9684
Myriad Genetic Laboratories, www.myriad.com or (800) 469-7423
National Cancer Institute, Cancer Genetics Services Directory, www.cancer.gov/search/genetics_services or (800) 4-CANCER [800-422-6237]
National Comprehensive Cancer Network, www.nccn.org or (888) 909-NCCN 
National Ovarian Cancer Coalition, www.ovarian.org or (888) OVARIAN [888-682-7246] or (561) 393-0005
National Society of Genetic Counselors, www.nsgc.org or (312) 321-6834
Women’s Cancer Network, www.wcn.org or (312) 578-1439