Women with BRCA1 and BRCA2 pathogenic variants were found to be at decreased risk for breast cancer for a 5-year period after undergoing elective risk-reducing salpingo-oophorectomy (RRSO), according to the results of a case series study published in JAMA Oncology.
Researchers gathered data from 876 families with known BRCA1 and BRCA2 mutations enrolled in the Breast Cancer Family Registry between 1996 and 2000. The average age at time of RRSO was 44.5 and 46.9 years for BRCA1 and BRCA2 families, respectively, while the average age at time of initial breast cancer diagnosis was 44.2 and 47.9 years, respectively.
The researchers analyzed the data with 3 different time-varying models to assess the effect of RRSO on breast cancer risk, specifically comparing a permanent exposure model that measures cumulative lifetime risk to several exponential decay models that assess how the impact of RRSO on breast cancer changes over time.
After undergoing RRSO, the women’s risk of developing breast cancer over the next 5 years dropped significantly, with hazard ratios of 0.28 (95% CI, 0.10- 0.63) and 0.19 (95% CI, 0.06-0.71) for women with BRCA1 and BRCA2 mutations, respectively. However, the researchers found that the protective benefit of RRSO weakened over time, with breast cancer risk hazard ratios increasing to 0.64 (95% CI, 0.38-0.97) and 0.99 (95% CI, 0.84-1.00) in BRCA1 and BRCA2 carriers once more than 5 years had passed.
The study also found that RRSO provided a reduced cumulative breast cancer risk in women with BRCA1 variants. These women decreased their risk of developing breast cancer by age 70 to either 48.2%, 48.8%, and 49.7%, respectively, depending on the women’s age when undergoing RRSO (aged 30, 35, or 40 years). In comparison, by age 70, women with BRCA1 mutations who did not undergo RRSO were found have a breast cancer risk of 60.1% (95% CI, 56.7 -66.0).
The researchers identified several limitations of the study: the exclusion of hormone replacement therapy after RRSO in the data analysis; the relatively small proportion of participants who underwent RRSO (6.3% of the BRCA1 group and 7.5% of the BRCA2 group); and the categorization of risk-reducing mastectomy as a censoring event as opposed to a competing risk event.
“Although the primary indication for RRSO is the prevention of [ovarian cancer], assessing its association with [breast cancer] risk is critical to guide clinical decision-making and the timing of such a decision,” the study researchers wrote. “The risk-benefit ratio of such a strategy needs also to be assessed carefully, because offering RRSO at a young age might induce adverse effects such as reduced quality of life, cardiovascular disease, or osteoporosis.”
Disclosure: Please refer to the original study for a full list of author’s disclosures.
Choi Y-H, Terry MB, Daly MB, et al. Association of risk-reducing salpingo-oophorectomy with breast cancer risk in women with BRCA1 and BRCA2 pathogenic variants. JAMA Oncol. Published online February 25, 2021. doi:10.1001/jamaoncol.2020.7995