Abstract PS3-02-12: Contralateral Breast Cancer Subtypes Mirror the Primary: A 23-Year Single-Center Cohort Study

Abstract Background Contralateral breast cancer (CBC) has traditionally been considered a newly developed, biologically independent tumor rather than a recurrence of the primary breast cancer. However, accumulating evidence suggests that some CBCs share molecular characteristics with the primary tumor, indicating possible biological relatedness. This study aimed to evaluate the biological association between primary and contralateral breast cancers by analyzing their subtype distribution and concordance patterns. Methods We analyzed 382 patients who underwent surgery for primary breast cancer at Seoul National University Hospital between 2001 and 2024 and subsequently developed contralateral breast cancer. Synchronous CBC was defined as contralateral breast cancer diagnosed simultaneously or within 6 months of primary invasive breast cancer diagnosis, while metachronous CBC was defined as contralateral breast cancer diagnosed thereafter. Patients with contralateral DCIS, unknown subtype, or initial distant metastasis were excluded. The study included 186 synchronous and 196 metachronous CBC cases. Subtype distributions of CBC were compared with those of sporadic breast cancers using multinomial exact tests. Additionally, subtype concordance between primary and contralateral tumors was evaluated using concordance rates. Results We identified distinct clinical patterns between synchronous and metachronous CBCs. Synchronous CBCs were more frequently associated with hormone receptor (HR) positive and HER2 negative primary tumors, whereas metachronous CBCs were more often associated with primary triple-negative breast cancer (TNBC) and showed stronger associations with BRCA mutation status.The subtype distribution of both metachronous and synchronous CBCs differed significantly from that of sporadic breast cancers (p<0.001), with a relatively higher proportion of TNBC. Subtype concordance between primary and CBC tumors was significantly higher than expected under a model of random subtype distribution among all subtypes (p < 0.001, concordance rate vs. expected rate: 79.7% vs. 63.1%, 32.0% vs. 5.5%, 30.8% vs. 10.5%, and 61.7% vs. 20.9% for HR+/HER2-, HR+/HER2+, HR-/HER2+, and TNBC, respectively) Conclusions Contralateral breast cancer does not arise as a random second primary event but rather reflects subtype-specific characteristics of the primary tumor. These findings indicate that the pathogenesis of CBC might not be an independent one but rather be primary tumor-dependent or host factor-dependent which warrants further investigation. Citation Format: E. Kang, C. Lee, H. Cho, D. Shin, J. Jung, H. Kim, H. Lee, W. Han, H. Moon. Contralateral Breast Cancer Subtypes Mirror the Primary: A 23-Year Single-Center Cohort Study [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 PS3-02-12.