Breast density changes after risk-reducing salpingo-oophorectomy in women with a pathogenic germline variant in BRCA1 or BRCA2

BACKGROUND: We studied changes in mammographic density (MD) among premenopausal women with a pathogenic germline variant (PGV) in the BRCA1 or BRCA2 gene, comparing those who did and did not undergo risk-reducing salpingo-oophorectomy (RRSO) in the interval between mammograms, accounting for changes in exogenous oral contraceptive or hormone replacement therapy (HRT) use.

METHODS: From five studies of the International BRCA1/2 Carrier Cohort Study consortium, we included 691 participants who had two or more screening mammograms available, were less than 47 years at the time of RRSO (N = 208), or premenopausal at all mammograms without RRSO (N = 483). MD metrics [percent density (PD), dense area (DA), and non-DA] were quantified using STRATUS. Multivariable linear mixed models assessed changes in MD metrics between groups, adjusting for confounders.

RESULTS: The mean PD at first mammogram was 26.8% ± 15.3 (RRSO) and 31.3% ± 18.1 (no RRSO). In a median 1.1 years between mammograms, PD decreased on average by 0.9% [95% confidence interval (CI), -1.6 to -0.2] among women who did not undergo RRSO in the interval between mammograms compared with 5.9% (95% CI, -7.4 to -4.5) among women who underwent RRSO in the interval (adjusted difference, -5.9%; 95% CI, -9.5 to -2.2; P = 0.002). Results were driven primarily by MD changes among BRCA2 PGV carriers. The use of HRT after RRSO attenuated the decline in PD.

CONCLUSIONS: On average, PD and DA decrease following RRSO in premenopausal carriers, particularly among BRCA2 PGV carriers. HRT formulation affects MD changes.

IMPACT: A decrease in MD may inform the potential protective effect of RRSO against breast cancer.