Undergoing prophylactic oophorectomy reduces all-cause mortality by 77% among women who carry a deleterious BRCA1 or BRCA2 genetic mutation, according to a report published online Feb. 24 in the Journal of Clinical Oncology.
The surgery’s protective effect stems largely from a reduction in the incidence of ovarian, tubal, and peritoneal cancers, "but there is an important component from reducing breast cancer incidence and mortality as well," reported Dr. Amy P.M. Finch of the University of Toronto and her associates in the Hereditary Ovarian Cancer Clinical Study Group.
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Undergoing prophylactic oophorectomy reduces all-cause mortality by 77% among women who carry a deleterious BRCA1 or BRCA2 genetic mutation, according to the report.
In addition, the results of this prospective cohort study support the recommendation that these women should undergo prophylactic oophorectomy by age 35, because their risk of developing cancer rises markedly after that, the investigators said.
Noting that the effect of oophorectomy on mortality has not been well studied and that the optimal age for undergoing the procedure hasn’t yet been determined, Dr. Finch and her colleagues analyzed data in an international registry of carriers of deleterious BRCA1 and BRCA2 mutations. Their study cohort included 5,783 women followed at 43 medical centers in Canada, the United States, Austria, France, Italy, Norway, and Poland, who were enrolled in 1995-2011.
Just under half of these women had a history of breast cancer, and the mean age at enrollment was 46 years (range, 30-88 years). They were followed for an average of 5.6 years for the development of cancer.
A total of 2,270 women did not undergo prophylactic oophorectomy, while 2,123 had already undergone the surgery at baseline and another 1,390 had it during the study period.
A total of 186 new ovarian, fallopian, and peritoneal cancers were diagnosed during follow-up. These included cases in 108 women with intact ovaries who were diagnosed clinically, 46 cases of occult cancer diagnosed at oophorectomy, and 32 cases of peritoneal cancer that developed after oophorectomy.
Of the 507 women who died during follow-up, 329 died from breast cancer; 67 died from ovarian, fallopian, or peritoneal cancer; 49 died from other cancers; 44 died of noncancer causes; and 18 died from unknown causes.
Oophorectomy had a profound protective effect on all-cause mortality and cancer-specific mortality, both for BRCA1 carriers and for BRCA2 carriers. Those who were cancer free at baseline and underwent the surgery showed a 77% reduction in all-cause mortality to age 70. Women who had a history of breast cancer at enrollment – including those whose mutation-carrier status was discovered when their breast cancer was diagnosed – showed a similar reduction in all-cause mortality after undergoing oophorectomy, the investigators reported (J. Clin. Oncol. 2014 Feb. 24 [doi: 10.1200/jco.2013.53.2820]).
The findings also support the current recommendation to undergo oophorectomy at age 35. "If a woman with a BRCA1 mutation chooses to delay salpingo-oophorectomy until age 40 years, we estimate that she will have a 4.0% chance of being diagnosed with ovarian cancer, either clinically before or at the time of salpingo-oophorectomy. If she chooses to wait until age 50 years, the probability rises to 14.2%," Dr. Finch and her associates said.
In view of this recommendation, "it is important that we ascertain the long-term effects of salpingo-oophorectomy and design effective treatments and preventive strategies for these," they added.
The researchers noted that their study began in 1995, before it was recommended that removal and detailed pathological evaluation of the fallopian tubes be included at oophorectomy. Eighteen of the 46 occult cancers discovered at surgery in this cohort were classified as primary fallopian tube cancers, which reinforces that the standard of care should now include removal of the tubes, they said.
This study was supported by the Canadian Breast Cancer Research Alliance, the National Institutes of Health, and the Ontario Ministry of Research and Innovation. Dr. Finch and her associates reported no financial conflicts of interest.