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. 2025 Oct;213(3):377-384.
doi: 10.1007/s10549-025-07787-3. Epub 2025 Jul 22.

Breast biopsies and breast cancer risk in Israeli BRCA germline pathogenic variant carriers

Dana Madorsky Feldman  1 , Miri Sklair-Levy  1   2   3 , Yael Laitman  4 , Renata Faermann  2   3 , Noam Nissan  2   3 , Osnat Halshtok Neiman  2   3 , David Samoocha  2   3 , Yael Yagil  2   3 , Eitan Friedman  5   6
Affiliations

Breast biopsies and breast cancer risk in Israeli BRCA germline pathogenic variant carriers

Dana Madorsky Feldman et al. Breast Cancer Res Treat. 2025 Oct.

Abstract

Purpose: Benign breast disease (BBD), particularly with proliferative changes, is a risk factor for breast cancer (BC) development in average risk women. There is a paucity of data on high-risk, BRCA1 and BRCA2 pathogenic variants (PVs) carriers.

Methods: Female BRCA1 and BRCA2 PV carriers treated at the Meirav Clinic, Sheba Medical Center between May 2011 and December 2024 were eligible. Data on in-hospital breast biopsies were retrieved following an ethically approved protocol. Statistical analyses included χ2 test (categorical variables) Mann-Whitney U test (continuous variables) and logistic regression for multivariate analysis.

Results: Overall, 1466 women (849 BRCA1 PV carriers) were monitored over 10,113 women/years. A total of 1453 biopsies were carried out in 454 participants (range 1-8 biopsies), with the majority (76.3%) benign and 242 (16.6%) malignant. Rates of BC in women undergoing at least two benign biopsies were correlated with the number of biopsies, being an older BRCA1 PV carrier, whereas having been diagnosed with fibroadenoma-seems not to increase BC risk.

Conclusions: In Israeli BRCA PV carriers, the number of biopsies, BRCA1 PV carriership were associated with an increased risk for developing BC, whereas fibroadenoma does not increase that risk. It is imperative to validate these preliminary observations.

Keywords: Atypia; BRCA PV carriers; Breast biopsy; Breast cancer; Histological instability; Proliferative and non-proliferative benign breast disease.

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Conflict of interest statement

Declarations. Conflict of interest: The authors have no conflicts of interest to declare that are relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Benign and malignant lesion distributions by biopsy and by mutated gene. Biopsy histological outcomes by gene. The numbers and % indicate the number of the total individuals and % of the total of individuals with the relevant histological subtypes diagnosed in the entire study
Fig. 2
Fig. 2
A Univariate analysis of the factors associated with prediction of BC risk in women who have had at least two benign biopsies. B Multivariate analysis of the same cohort
Fig. 3
Fig. 3
Time elapsed between first and second biopsy and *interval12—time (years) between the first and second biopsy; *interval23—time (years) between the second and third biopsy
See this image and copyright information in PMC

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