Breast Cancer Protection Afforded by Oophorectomy Differs in BRCA1, BRCA2 Carriers
NEW YORK (Reuters Health) – Findings from a large prospective study suggest that bilateral oophorectomy reduces the risk of breast cancer in premenopausal BRCA2, but not BRCA1 mutation carriers, although the findings “warrant further evaluation,” researchers caution.
“Whether or not bilateral oophorectomy reduces breast cancer risk among women with a BRCA1 or BRCA2 mutation carriers is a matter of debate,” note Dr. Steven Narod of Women’s College Research Institute and Hospital, Toronto, Canada and colleagues in their report, online September 6 in the Journal of the National Cancer Institute.
To investigate further, they studied more than 3,700 women with a BRCA1 or BRCA2 mutation, with no history of cancer, who had both breasts intact, and for whom they had information on oophorectomy status; 1,552 women had a bilateral oophorectomy and 2,170 did not. The women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death.
During an average follow-up of 5.6 years, 350 new first primary breast cancers were diagnosed. Of these, 143 (41%) had an oophorectomy prior to the diagnosis of breast cancer.
Overall, the annual incidence of breast cancer was 1.7%, with similar estimates in women with and without oophorectomy. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with the risk of breast cancer compared with women who did not undergo oophorectomy. The age-adjusted hazard ratio was 0.91 and the multivariable HR was 0.89.
When stratified by BRCA mutation status, the annual incidence of breast cancer was 1.7% for BRCA1 and 1.5% for BRCA2 mutation carriers. The age-adjusted HR associated with oophorectomy was 0.96 (p=0.76) for BRCA1 and 0.65 (p=0.14) for BRCA2 mutation carriers.
When stratified by age at diagnosis, oophorectomy was not significantly associated with the risk of breast cancer prior to age 50 in women with a BRCA1 mutation (HR, 0.79).
In contrast, oophorectomy was associated with a statistically significant 82% reduction in breast cancer diagnosed prior to age 50 in women with a BRCA2 mutation (HR, 0.18) but did not protect against breast cancer diagnosed after age 50 (HR, 1.20).
“However, this was based on only three cases in the oophorectomy group with an annual risk of 0.5%,” the researchers say.
They had information on estrogen receptor (ER) status for 41 of the 57 BRCA2 cases. The protective effect of oophorectomy on breast cancer diagnosed prior to age 50 years among ER-positive cases was “very strong” (HR, 0.10). They didn’t have enough data to evaluate the relationship for ER-negative cases.
The researchers say this is “largest prospective study to date evaluating the magnitude of protection associated with oophorectomy among BRCA mutation carriers.”
“Our findings have important clinical implications,” they add. “BRCA mutation carriers face high lifetime risks of developing breast, ovarian, and contralateral breast cancer. Although we failed to show an effect of oophorectomy on breast cancer overall, bilateral salpingooophorectomy should be recommended at age 35 years for BRCA1 mutation carriers and at age 40 years for BRCA2 mutation carriers. This is based on the ages at which the annual rates for ovarian cancer start to rise. The protective role of oophorectomy diagnosed prior to age 50 years further supports recommendations at age 40 years for BRCA2 mutation carriers. Additional studies with longer follow-up are warranted.”
J Natl Cancer Inst 2016.