In women with a BRCA1 or BRCA2 mutation, oophorectomy reduces the risk of ovarian and breast cancer; however, the ideal age at which these women should undergo the procedure has not been known. Now, new research from Women’s College Hospital in Toronto suggests that delaying oophorectomy beyond age 35 results in a significantly increased risk of developing ovarian cancer.
The research team, led by Amy Finch, PhD, and Steven Narod, MD, used questionnaires and medical records to follow 5,783 women with BRCA1 or BRCA2 mutations for a mean of 5.6 years. These questionnaires gathered data on reproductive history, surgical history (including preventive oophorectomy and mastectomy), and hormone use. Women from seven countries in North America and Europe participated.
Substantial Reductions in Cancer Incidence and Mortality
Throughout follow-up, 186 new ovarian, fallopian, and peritoneal cancers were diagnosed, including 46 occult cancers—asymptomatic disease that was discovered during prophylactic oophorectomy. Occult cancers were detected in 4.2% of BRCA1 carriers and 0.6% of BRCA2 carriers.
Among women with intact ovaries, the annual rate of cancer diagnosis was 0.91% in BRCA1 carriers and 0.30% in BRCA2 carriers. BRCA1 carriers were at highest risk between age 50 and 59 years, whereas BRCA2 carriers were at highest risk between age 60 and 69 years.
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Prophylactic oophorectomy reduced the risk of ovarian, fallopian tube, or peritoneal cancer by 80%.
Oophorectomy was also clearly associated with reduced risk of death. Among women who were cancer-free at entry into the study, oophorectomy reduced all-cause mortality during the study period by 77%.
Women who had previously been treated for breast cancer also benefited from oophorectomy: the risk of death from any cause was reduced by 61% in women who underwent oophorectomy before or within 3 years of breast cancer diagnosis and by 76% in women who underwent oophorectomy more than 3 years after diagnosis.
Women whose ovarian cancer was detected during oophorectomy had a much better 5-year survival rate than those whose cancer was detected clinically (91.6% vs 54.4%; P<0.01).
When Is the Right Age for Oophorectomy?
“Scientific evidence clearly shows removal of a woman’s ovaries and fallopian tubes is very effective in preventing both breast and ovarian cancer in women with a BRCA mutation,” said Dr. Finch, “but the real question has been at what age these women should have the surgery to best diminish their chance of developing cancer.”
Currently, oophorectomy is recommended for BRCA1 carriers at age 35. The study authors calculated that a woman who waits until age 40 has a 4.0% chance of being diagnosed with ovarian cancer, either clinically or during oophorectomy, and that a woman who waits until age 50 has a 14.2% chance of an ovarian cancer diagnosis.
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“Our study supports the notion that women who carry a BRCA gene mutation will have a much lower risk of developing or dying from cancer if they have an oophorectomy at age 35,” said Dr. Narod.
Oophorectomy results in premature menopause and may have other effects on a woman’s health, Dr. Finch pointed out. “After an oophorectomy, the long-term effects on a woman’s cardiovascular health and her bone health are less well known, and further research is needed.”
- Finch APM, Lubinski J, Møller P, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014 Feb 24. [Epub ahead of print]