Oophorectomy can reduce ovarian cancer risk in women with BRCA mutations
Patients benefit from counseling, support
When Tamar Goldwaser, MD, of Montefiore Medical Center in New York City, counsels patients who test positive for the BRCA1 or BRCA2 genetic mutations, she tells them about their risk for developing ovarian cancer. Then she explains how a risk-reducing, bilateral salpingo-oophorectomy (RRBSO) can reduce that risk.
“The risk of developing ovarian cancer for a woman who has a positive BRCA1 mutation can be as high as 35% to 46%,” says Dr. Goldwaser, an obstetrician-gynecologist in Montefiore's reproductive genetics department. “Evidence shows that an RRBSO for a high-risk woman reduces that risk to 5%.” Although the risk of ovarian cancer with the BRCA2 gene is somewhat lower (15% to 25%), an RRBSO can lower that risk to close to 0%, she adds.
In all, women with BRCA1/BRCA2 mutations achieve an 80% to 90% reduction in their lifetime risk of ovarian cancer, as well as a 50% to 60% reduction in risk of breast cancer if RRBSO is performed prior to menopause. Adding to the literature, a recent study of more than 3000 women younger than 50 years in the Polish Hereditary Breast Cancer Consortium found that women with BRCA1-mutated breast cancer, particularly those mutation carriers who underwent oophorectomy, lived just as long as women who were not BRCA carriers. The oophorectomy reduced the hazard risk by 70%.
High-risk women who elect not to undergo RRBSO can instead opt to undergo screening, which includes serum CA125 evaluation and transvaginal ultrasound every 6 months, but these techniques have not been shown to either effectively detect early-stage disease or to affect mortality. “Removal of both the ovaries and the fallopian tubes is something we do recommend, because there's such great evidence that it reduces risk, and the earlier you do it the better,” says Dr. Goldwaser. “We recommend that women try to do it either between the ages of 35 to 40 [years] or when they have completed their childbearing.”
That approach is recommended by the National Comprehensive Cancer Network (NCCN) and other professional organizations, and the NCCN adds that these recommendations should occur within a counseling process that evaluates all the benefits, risks, and results of surgery. Although the procedure has now become standard of care for women at high risk of developing ovarian cancer, it is not without some challenges. For premenopausal women, the surgery puts them into premature menopause, and can carry all of the accompanying problems of hot flashes, decreased libido, and earlier risk of osteoporosis. At the same time, some studies have shown that it can increase the risk of all-cause mortality, cardiovascular disease, stroke, lung cancer, cognitive impairment or dementia, parkinsonism, osteoporosis, depressive or anxiety symptoms, and sexual dysfunction.[3, 4] For these reasons, authors of a 2010 article recommended that the procedure not be performed on women who are not at high risk for developing the disease.
Support and Stress Management
At the same time, less is known about how RRBSO affects a woman's quality of life. When Bonnie McGregor, PhD, a cancer prevention researcher at the Fred Hutchinson Cancer Research Center in Seattle, Washington, learned that physicians in the high-risk clinic at the Seattle Cancer Care Alliance wanted more information to provide their patients about how they would feel after undergoing the surgery, she decided to conduct a study on the topic.
She and colleagues analyzed questionnaires completed by 119 women at high risk for ovarian cancer at 2, 6, and 12 months after undergoing RRBSO, and specifically looked at their physical and emotional functioning. The researchers measured reported problems such as menopausal symptoms, sleep problems, and “trait” (a stable personality feature) versus “state” (how a person is feeling at the moment) anxiety. Results indicated that the women who were less bothered by menopausal and other emotional and physical symptoms after surgery were those with lower trait anxiety, higher optimism, and stronger support. At the same time, she found that cancer risk perceptions, cancer worry, and general distress declined significantly after surgery.
Since we don't have a really good way to diagnose ovarian cancer, RRBSO seems like the best course of action.
—Bonnie McGregor, PhD
“Since we don't have a really good way to diagnose ovarian cancer, RRBSO seems like the best course of action,” she says. “For women who participated in the study, they felt strongly that they needed to reduce their risk.” Her findings show that most women do fairly well after the surgery, particularly if they have social support and ways to manage their stress.
Another study by Carolyn Fang, PhD, of the division of population science at Fox Chase Cancer Center in Philadelphia, Pennsylvania, compared the quality of life women at high risk for ovarian cancer who underwent RRBSO with a control group of women who were only screened for the disease. Although the women who had the surgery experienced short-term quality of- life problems such as poorer physical functioning, more physical role limitations, greater pain, less vitality, poorer social functioning, hot flashes, and vaginal dryness, most of those deficits were recovered after 6 to 12 months.
For women at high risk of ovarian cancer who opt not to have the surgery, “doctors have to be reminded not to be falsely reassured by screening,” Dr. Goldwaser says. Each patient has to be taken on a case-by-case basis depending on their individual risk circumstances, she adds, noting that if a woman is 35 years of age and still wants to have children, “we tell her not to delay and then not to delay in between if she wants another” so that she can have the surgery sooner rather than later. As an alternative, a woman can choose to have in vitro fertilization (IVF) and freeze her embryos or undergo egg or ovary freezing (known as ovarian cryopreservation, which is still experimental).
Patients who have lost a family member to ovarian cancer are more likely to opt for the surgery immediately whereas others may wait, although more than half the patients she counsels do eventually have the surgery. “Patients we counsel have to understand that they could get a diagnosis of cancer at the time of the oophorectomy,” Dr. Goldwaser says. “Then, the surgery gets converted to a full hysterectomy in which the uterus is removed along with lymph nodes and the cervix.”
In patients older than 45 years who have BRCA mutations, the risk of finding an occult ovarian or fallopian tube cancer at the time of surgery is about 20%. In younger women, it's about 5% to 8%, she says.