1. Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers.
- Author
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Lee JY, Lee JW, Chung MS, Choi JG, Sim SH, Kim HJ, Kim JE, Lee KE, Park YH, Kang MJ, Ahn MS, Chae YS, Park JH, Kim JH, Kim GM, Byun JH, Park KU, Kim JW, Jung SP, Lee JH, An JS, Jang B, Yoon D, Kim J, Hong J, Koo H, Cho KR, Kim CY, Sa JK, and Park KH
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Middle Aged, Age Factors, Class I Phosphatidylinositol 3-Kinases genetics, East Asian People genetics, GATA3 Transcription Factor genetics, Receptor, ErbB-2 genetics, Breast Neoplasms genetics, Mutation
- Abstract
Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive., Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities., Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy., Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients., (© 2024. The Author(s).)
- Published
- 2024
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