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Oophorectomy may decrease BRCA1-mutated breast cancer mortality
Women with ER-negative breast cancer who harbor BRCA1 mutations may experience a survival benefit from undergoing oophorectomy, according to the results of a retrospective analysis.
“Women who carry a germline mutation in either the BRCA1 or BRCA2 gene face a lifetime risk of breast cancer of up to 70%, and once they receive a diagnosis of breast cancer, they face high risks of both second primary breast and ovarian cancer,” Steven A. Narod, MD, of the Women’s College Research Institute, and colleagues wrote. “Preventive salpingo-oophorectomy is recommended to women with a BRCA mutation at age 35 years or thereafter to prevent breast and ovarian cancer, but the benefit of oophorectomy may extend to reducing mortality from breast cancer as well.”
Steven A. Narod
Narod and colleagues conducted a retrospective analysis of families who received counseling at one of 12 clinical genetics centers. The families had a documented BRCA1 or BRCA2 mutation and at least one documented case of invasive breast cancer.
The analysis included 676 women from the families who were diagnosed between 1975 and 2008 with stage I or II breast cancer and who were aged 65 years or younger. Women with a previous cancer diagnosis (including breast cancer) were excluded from the analysis.
Women chose to undergo oophorectomy after breast cancer diagnosis (n = 345) or to forgo the procedure (n = 331). The mean time to oophorectomy from diagnosis was 6.1 years (range, 0.1-31.8).
Researchers noted the 20-year survival rate across the entire cohort was 77.4%.
Analyses adjusted for several factors including age and year at diagnosis, BRCA gene, tumor size, nodal and ER status, and chemotherapy and tamoxifen use indicated oophorectomy was associated with a 54% reduction in breast cancer-specific mortality (HR = 0.46; 95% CI, 0.27-0.79).
Nine women died of ovarian cancer in the cohort that did not undergo ovary removal. Oophorectomy was associated with a 65% reduction in all-cause mortality (HR = 0.35; 95% CI, 0.22-0.56).
Women with a BRCA1 mutation demonstrated a significant reduction in disease-related mortality after ovary removal (HR = 0.38; 95% CI, 0.19-0.77), particularly if they underwent the procedure within 2 years of cancer diagnosis vs. not undergoing the procedure (HR = 0.27; 95% CI, 0.11-0.66). However, oophorectomy was not associated with a statistically significant reduction in breast cancer-specific mortality among women with a BRCA2 mutation (HR = 0.57; 95% CI, 0.23-1.43).
Researchers did not observe a significant difference in outcomes related to stage of disease or receipt of chemotherapy in women with BRCA1 mutations who underwent ovary removal. The reduction in risk for breast cancer-related death associated with oophorectomy was evident among BRCA1 carriers immediately after surgery and persisted for 15 years.
Women with ER-negative breast cancer strongly benefited from oophorectomy (HR = 0.07; 95% CI, 0.01-0.51). Among women aged 50 years or older with ER-negative breast cancer, none of those who underwent oophorectomy died compared with 21% (n = 3) who did not undergo the procedure.
“It is important that follow-up studies be performed on women who undergo oophorectomy as part of their initial treatment, in particular those women who undergo oophorectomy in their first year after diagnosis,” Narod and colleagues concluded. “It is also important that our observations be confirmed in other study populations. Further data are needed, in particular for BRCA2 carriers, in order to confirm the benefit of oophorectomy in this population.”
The results of this study suggest that oophorectomy should become a permanent part of the physician–patient conversation after a breast cancer diagnosis, Mary L. Disis, MD, editor-in-chief of JAMA Oncology, professor of medicine at the University of Washington, Seattle, and a member of the Fred Hutchinson Cancer Research Center, wrote in an accompanying editorial.
“The hazard ratio was further reduced … if the surgery was performed within 2 years of the breast cancer diagnosis,” Disis wrote. “The data reported here are compelling and suggest that the potential of oophorectomy should become part of the treatment discussion at the time of diagnosis for BRCA mutation carriers with early-stage breast cancers.” – by Cameron Kelsall
Disclosure: The researchers report no relevant financial disclosures. Disis reports research funding from EMD Serono, Seattle Genetics and VentiRx and stock ownership in EpiThany and VentiRx.