Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 1;34(8):1295-1305.
doi: 10.1158/1055-9965.EPI-25-0218.

Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Elizabeth A Loehrer #  1 , Frederieke H van der Baan #  2   3 , Thea M Mooij  2 , Nadine Andrieu  4   5   6   7 , Antonis C Antoniou  8 , Monique D Dorrius  9 , Douglas F Easton  8   10 , Christoph Engel  11 , Karin Kast  12 , Ritse M Mann  13   14 , Catherine Noguès  15   16 , Rita K Schmutzler  12 , Yen Y Tan  17 , Mikael Eriksson  18 , Carla H van Gils  19 , Maartje J Hooning  20   21 , Matti A Rookus  2 , Marjanka K Schmidt  1   22
Affiliations

Breast Density Changes after Risk-Reducing Salpingo-oophorectomy in Women with a Pathogenic Germline Variant in BRCA1 or BRCA2

Elizabeth A Loehrer et al. Cancer Epidemiol Biomarkers Prev. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

E.A. Loehrer reports grants from Dutch Cancer Society (KWF) during the conduct of the study. A.C. Antoniou reports other support from Cambridge Enterprise outside the submitted work. D.F. Easton reports grants from Cancer Research UK during the conduct of the study. C. Engel reports grants from German Cancer Aid and Federal Ministry of Education and Research during the conduct of the study. R.M. Mann reports grants, personal fees, and nonfinancial support from Siemens Healthineers, Beckton & Dickinson, and ScreenPoint Medical, grants and personal fees from Bayer Healthcare, nonfinancial support from Koning and Lunit, and grants and nonfinancial support from PA Imaging outside the submitted work. R.K. Schmutzler reports grants from German Cancer Aid and German Ministry of Education and Research during the conduct of the study. Y.Y. Tan reports other support from MSD, Pfizer, Gilead Sciences, Amgen, and AstraZeneca and nonfinancial support from SOPHiA Genetics outside the submitted work. C.H. van Gils reports grants from EU TRANSCAN during the conduct of the study, as well as grants from Bayer Healthcare, Hologic, Siemens Healthineers, and ZonMw outside the submitted work. M.K. Schmidt reports grants from KWF during the conduct of the study. No disclosures were reported by the other authors.

Figures

Figure 1.
Figure 1.
Exclusion criteria leading to the final study population. A flow chart starting with all available mammograms and demonstrating the number of mammograms and/or individuals that were excluded from the analysis and the reason for their exclusion is shown. Note that 208 mammogram pairs capture the interval in which RRSO occurred, and 63 women with RRSO additionally contribute 137 mammogram pairs prior to the occurrence of their RRSO. AU, Austria; BC, breast cancer; FR, France; GE, Germany; NL, the Netherlands.
See this image and copyright information in PMC

References

    1. Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007;356:227–36. - PubMed
    1. McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2006;15:1159–69. - PubMed
    1. Lynge E, Vejborg I, Lillholm M, Nielsen M, Napolitano G, von Euler-Chelpin M. Breast density and risk of breast cancer. Int J Cancer 2023;152:1150–8. - PMC - PubMed
    1. Bodewes FTH, van Asselt AA, Dorrius MD, Greuter MJW, de Bock GH. Mammographic breast density and the risk of breast cancer: a systematic review and meta-analysis. Breast 2022;66:62–8. - PMC - PubMed
    1. Boyd NF, Martin LJ, Yaffe MJ, Minkin S. Mammographic density and breast cancer risk: current understanding and future prospects. Breast Cancer Res 2011;13:223. - PMC - PubMed