Abstract PS3-03-25: Alteration in estrogen receptor status in metachronous contralateral breast cancer among unilateral early breast cancer patients with BRCA 1/2 mutations

Abstract Background BRCA1/2 mutations are known to significantly increase the risk of contralateral breast cancer (CBC). However, their influence on changes in estrogen receptor (ER) status between primary breast cancer and metachronous CBC remains unclear. This study investigates ER status alterations in CBC patients with BRCA1/2 mutations to provide insights into their clinical implications. Methods This multicenter retrospective study was conducted between 2004 and 2020. Patients with unilateral early breast cancer who underwent BRCA1/2 testing and developed metachronous CBC were grouped by BRCA1/2 mutation status. ER status of primary and CBC tumors was compared using Fisher’s exact test and logistic regression to assess the relationship between BRCA1/2 mutations and ER alterations. Results Among 423 CBC patients, those with BRCA1 mutation had a higher likelihood of ER negative primary tumors transitioning to ER negative CBC (70.7%) compared to BRCA1/2 negative patients (odds ratio [OR] 3.8, p < 0.001). Similarly, ER-negative primary tumors were more likely to remain ER negative in CBC among BRCA1 or BRCA2 mutation carriers (64.8%, OR 2.9, p = 0.002). These findings demonstrate a strong association between BRCA1 mutations and the development of ER negative CBC in ER negative primary breast cancer. Of the patients with primary ER-negative breast cancer, those who received adjuvant chemotherapy for both primary and contralateral breast cancers showed a significantly higher rate of CBC with ER-negative alteration (OR 4.23, p=0.001). Conclusion BRCA1 mutation carriers face a significantly higher risk of developing ER negative metachronous CBC, in ER negative primary tumor. These findings highlight the importance of genetic counseling and risk-reducing strategies, including prophylactic mastectomy, for BRCA1 mutation carriers, which typically requires more aggressive treatments. Citation Format: K. Kim, E. Kang, S. Baek, H. Lee, S. Ahn, W. Park, D. Shin, H. Lee, S. Nam, S. Kim, J. Yu, B. Chae, L. Se Kyung, J. Lee, J. Ryu. Alteration in estrogen receptor status in metachronous contralateral breast cancer among unilateral early breast cancer patients with BRCA 1/2 mutations [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-03-25.