BRCA mutations in Korean hormone receptor-positive, HER2-negative breast cancer patients were associated with a 3.55-fold higher odds of high-risk multigene assay results.
Is BRCA mutation associated with high-risk classification on multigene assays in patients with hormone receptor-positive, HER2-negative breast cancer?
In Korean patients with HR+/HER2- breast cancer, the presence of a BRCA mutation is significantly associated with a high-risk classification on multigene assays.
Abstract Purpose BRCA mutations significantly increase the lifetime risk of breast cancer. While they are strongly associated with triple-negative breast cancer, they are also found in hormone receptor-positive, HER2-negative subtypes, in which multigene assays are commonly used for risk stratification and treatment decision-making. However, the relationship between BRCA status and multigene assay outcomes remains unclear, particularly in Asian populations. This study investigates the association between clinical indications for BRCA testing and multigene assay results in Korean breast cancer patients. Methods This multicenter study included 2,542 patients with hormone receptor-positive, HER2-negative breast cancer who underwent multigene testing between 2013 and 2024. BRCA testing was performed in patients aged under 40 years, those with bilateral breast cancer, or those with a personal or family history of breast or ovarian cancer within third-degree relatives. Multi-gene assays included Oncotype DX, MammaPrint, EndoPredict, and OncoFREE, and each result was classified into high-risk or low-risk groups based on each test-specific criteria. Statistical analyses were performed using chi-square tests and logistic regression in SPSS. Results Patients were categorized as BRCA-tested group (n=798) or non-tested group (n = 1,596). In the BRCA-tested group, 19.5% were classified as high risk and 80.5% as low risk by multigene assay. pTstage, pNstage, histologic grade, progesterone receptor status, and Ki-67 level was independently associated with high risk and multigene assay result. BRCA mutation was identified in 44 patients (7 BRCA1 mutation, 37 BRCA2 mutation). BRCA mutation was independently associated with high-risk classification on multigene assay (OR 3.554, 95% CI 1.767-7.151, p 0.001). In subgroup analysis of BRCA mutation group, among 30 patients with a family history, 20 (66.7%) were classified as high risk. Multivariate analysis also confirmed that familial history of breast or ovarian cancer was independently associated with high-risk in BRCA-mutation patients. (OR 9.752, 95% CI 1.449-65.651, p 0.05). An association between BRCA testing indications and high-risk multigene assay results was not statistically significant when only one indication was present. Conversely, the presence of two or more indications demonstrated a potential correlation with high-risk classification. (OR 5.282, p 0.061) Conclusion In Korean patients with hormone receptor-positive, HER2-negative breast cancer, BRCA mutation was significantly associated with high-risk classification on multigene assay. In BRCA-mutated patients, the presence of a family history further increased the likelihood of high-risk classification. Additionally multiple BRCA testing indications predicted high-risk classification in BRCA mutation patients, but this trend was not observed in those without a detected mutation. Citation Format: S. Lee, S. Lee, I. Lee, S. Park, J. Kim, N. Son. Association of clinical BRCA testing with multigene assay results 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 PS4-03-07.
Lee et al. (2026) studied this question. BRCA mutations in Korean hormone receptor-positive, HER2-negative breast cancer patients were associated with a 3.55-fold higher odds of high-risk multigene assay results.
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