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.