Salpingo-Oophorectomy Associated With Reduced Breast Cancer Risk in Patients With BRCA1/2 Pathogenic Variants

In the immediate 5 years after surgery for women carrying BRCA1 and BRCA2 pathogenic variants, research found that a lowered risk of breast cancer was associated with risk-reducing salpingo-oophorectomy (RRSO), according to data published in JAMA Oncology.

More, the research found a longer-term association with cumulative breast cancer risk in patients carrying BRCA1 pathogenic variants.

“Our findings may have important clinical implications for the treatment of women with BRCA1 or BRCA2 pathogenic variants. 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,” wrote the investigators. “Our results suggest a reduced [breast cancer] risk associated with RRSO in women carrying BRCA1 and BRCA2 pathogenic variants, but the association with cumulative risk was stronger among women carrying BRCA1 pathogenic variants.”

The primary analysis included 876 families, 498 of whom had BRCA1 (n = 2650) and 378 with BRCA2 (n = 1925) varients. Within 5 years after surgery, RRSO was associated with a reduced risk of breast cancer for carriers of BRCA1 (HR, 0.28; 95% CI, 0.10-0.63) and BRCA2 (HR, 0.19; 95% CI, 0.06-0.71). The hazard ratios were weaker when analyzing the associations after 5 years post-surgery (HR, 0.64; 95% CI, 0.38-0.97; and HR, 0.99; 95% CI, 0.84-1.00, respectively).

By age 70 years, the cumulative risk of breast cancer was 49.7% (95% CI, 40.0%-60.3%) for BRCA1 pathogenic variant carriers and 52.7% (95% CI, 47.9%-58.7%) for BRCA2 pathogenic variant carriers who underwent RRSO at age 40 years. In comparison, women without RRSO had a cumulative risk of breast cancer of 61.0% (95% CI, 56.7%-66.0%) and 54.0% (95% CI, 49.3%-60.1%) for BRCA1 and BRCA2 carriers, respectively.

Overall, the primary end point for all analyses were the time to a first primary breast cancer.

“The evaluation of RRSO uptake and its timing in association with [breast cancer] risk is critical for the clinical management of women carrying pathogenic variants in BRCA1 and BRCA2 genes,” wrote the investigators. “Our study brings new insights by investigating [breast cancer] risk after RRSO in a large series of BRCA1 and BRCA2 pathogenic variant carrier families from the [Breast Cancer Family Registry] and by additionally assessing the time-varying association of RRSO with [breast cancer through specifically examining the permanent exposure hypothesis.”

The analysis was a case series investigating the association of RRSO with the risk of breast cancer for women with these pathogenic variants. Families enrolled in the Breast Cancer Family Registry between 1996 and 2000 that carried a pathogenic variant in BRCA1 or BRCA2 were included in the study’s population. The study design specifically assessed the time-varying association of RRSO with breast cancer risk, while also accounting for potential biases.

One of the main methodological limitations explained by the research team centers around risk-reducing mastectomy, which the team assumed was a random censoring event for breast cancer, but acknowledged it as a possible alternative risk event. More, the data were limited because the team did not consider hormone replacement therapy after RRSO.

“Further work is needed to confirm this result in larger cohorts and to assess carefully the optimal timing of RRSO uptake,” concluded the investigators.

Reference:

Choi YH, 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