• Ji Yoon Lee, Ji Won Lee, Min Sung Chung, Jong Gwon Choi, Sung Hoon Sim, Hyo Jeong Kim, Jeong Eun Kim, Kyoung Eun Lee, Yeon Hee Park, Myoung Joo Kang, Mi Sun Ahn, Yee Soo Chae, Ji Hyun Park, Jee Hyun Kim, Gun Min Kim, Jae Ho Byun, Keon Uk Park, Ju Won Kim, Seung Pil Jung, Jung Hyun Lee, Jung Seok An, Byunghyun Jang, Dayoung Yoon, Jiwon Kim, Jisoo Hong, Harim Koo, Kyu Ran Cho, Cheol Yong Kim, Jason K Sa, and Kyong Hwa Park.
• Department of Biomedical Informatics, Korea University College of Medicine, Seoul, Republic of Korea.
• Bmc Med. 2024 Sep 27; 22 (1): 422422.

BackgroundBreast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive.MethodsIn 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.ResultsWe 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.ConclusionsOur 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).

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