Women with BRCA-positive breast cancer benefit from ovary removal23 Apr 2015
A review of 700 BRCA-positive breast cancer cases showed that women who remove their ovaries (with a prophylactic bilateral oophorectomy) have significantly lower risk of death. The benefit is particularly strong in BRCA1 carriers (62% lower) compared to BRCA2 (43% lower).
The risk reduction jumped to 93% for estrogen receptor-negative breast cancers, which account for a majority of BRCA1-positive breast cancers. The risk reduction associated with BRCA2 did not achieve statistical significance.
First study to show mortality risk reduction
The study is the first to show a reduction in breast cancer mortality risk in women who undergo prophylactic oophorectomy after diagnosis of BRCA-positive breast cancer, as reported online in JAMA Oncology.
"In this study, we confirm that women with breast cancer and a BRCA1 mutation improve their prognosis if they undergo oophorectomy and that the protective effect of the oophorectomy persists beyond age 50 years," Steven A. Narod, MD, of Women's College Research Institute in Toronto, and co-authors concluded.
"In previous studies, we have shown that oophorectomy reduces the risk of both ovarian and breast cancers, and we now report that the benefits of oophorectomy include a reduction in the risk of breast cancer mortality."
70% lifetime risk of breast cancer with BRCA1 or BRCA2
A germline mutation in BRCA1 or BRCA2 confers as much as a 70% lifetime risk of breast cancer. Women who develop BRCA-positive breast cancer have a high risk of second primary breast cancers and ovarian cancer. Several groups recommend prophylactic salpingo-oophorectomy for BRCA carriers at age 35 or older to reduce the risk of breast and ovarian cancer, but the benefits of ovary removal may include a reduced risk of dying of breast cancer, the authors noted in their introduction.
Research increasingly focusing on genetic mutations
Recent studies have shown reductions in all-cause mortality before age 70 among carriers of BRCA mutations who undergo oophorectomy and in breast cancer-specific mortality.
"These two studies imply that if an oophorectomy is performed after a diagnosis of breast cancer, then mortality is reduced, but neither study adjusted for stage of cancer at diagnosis or for other treatments received," the authors noted.
Another recent study limited to women with early-stage breast cancer showed a 70% lower breast cancer mortality after oophorectomy among carriers of BRCA1. Two other studies showed a reduced mortality risk following oophorectomy in carriers of BRCA mutations and a history of breast cancer.
Continuing the investigation into potential benefits of prophylactic oophorectomy, Narod and colleagues analyzed data from records of 676 women with early breast cancer and known BRCA status. The patients were identified through 10 genetics clinics that had counseled the women or their families.
Women included in the analysis had diagnoses of stage 1 or 2 breast cancer at 65 or younger during 1975 to 2008. The study population consisted of 608 women proven to be carriers of a BRCA mutation and 68 women who were not tested for BRCA status but presumed to be gene carriers because of family history. Women who underwent oophorectomy prior to breast cancer diagnosis were excluded from the analysis.
The primary endpoint was breast cancer mortality during a 20-year follow-up period. The authors found that 128 women died of breast cancer during the follow-up period.
The data showed that 407 women underwent oophorectomy after breast cancer diagnosis and 269 did not. Seven women underwent oophorectomy after distant recurrence and 55 women after diagnosis of ovarian cancer. Those 62 patients were included in the no-oophorectomy group, leaving 345 patients in the oophorectomy group.
Among women who had oophorectomy, 219 (64.4%) were BRCA1 carriers and 121 (35.6%) were BRCA2 carriers.
An adjusted analysis showed a 54% reduction in breast cancer-specific mortality in association with oophorectomy.
Women who were BRCA1 carriers had a statistically significant 62% reduction in the risk of breast cancer mortality after oophorectomy. A 43% risk reduction among BRCA2 carriers did not achieve statistical significance.
Oophorectomy was associated with a 65% reduction in all-cause mortality compared with no oophorectomy during the 20-year follow-up period.
Comment: "pretty strong evidence" of benefit
The study provides "pretty strong evidence that women with BRCA1 mutations (and probably BRCA2 mutation carriers) benefit from having their ovaries removed," said Robert Debernardo, MD, of the Cleveland Clinic, who was not involved in the study.
"The most interesting data they present is the risk reduction in women with ER-negative breast cancers," Debernardo told MedPage Today by email. "The risk reduction is very large, which seems counterintuitive, but extremely important since these tend to be the most high-risk and more difficult to treat breast cancers. In the end, the significance of this paper will be that it will likely change clinical practice."
The study does have limitations, beginning with the shortcomings inherent to a retrospective data analysis, he added. Additionally, breast cancer patients today often receive aromatase inhibitors to improve their prognosis, and the drugs were not available during most of the study's time period.