Prevalence of Incidental Breast Cancer and Precursor Lesions in Carriers of Pathogenic Germline Variants Undergoing Risk-Reducing Mastectomy

Background/Aim: Precursor lesions, including B3 lesions of uncertain malignant potential, preinvasive lesions such as ductal carcinoma in situ (DCIS), and invasive lesions identified in the breast tissue of carriers of pathogenic germline variants undergoing risk-reducing breast surgery, have received limited attention to date. This study aimed to assess the prevalence and histopathological features of these lesions, considering their genetic, demographic, and radiological characteristics. Patients and Methods: We performed a retrospective monocentric cohort study analyzing 169 healthy women and patients after previous breast cancer who carried pathogenic germline variants in BRCA1/2, PALB2, and CHEK2. These individuals underwent primary bilateral or contralateral risk-reducing mastectomy (RRM) at the Department of Gynecology with Breast Center Charité – Universitätsmedizin Berlin between 2014 and 2021. Results: We detected a low prevalence of precursor lesions (n=11; 6.5%) and a very low prevalence of preinvasive (n=1) and invasive lesions (n=2; total 1.8%) in the breast tissue following RRM. Flat epithelial atypia (FEA) emerged as the predominant precursor lesion. Invasive lesions were infrequent, with only two cases of invasive breast cancer identified, both in patients who did not undergo preoperative MRI scans. Conclusion: The study highlights the critical need for rigorous surveillance programs and advanced imaging protocols, particularly tailored to younger women at elevated risk of breast cancer, to ensure early detection of occult lesions. The implementation of interdisciplinary counseling and precise timing of risk-reducing mastectomy is essential to reduce the progression to preinvasive and invasive disease.