Abstract PO1-15-11: Molecular and clinical disparities in breast cancer among East Asian populations

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. Method We aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. We explored the unique molecular profiles of breast cancer patients by categorizing them into two distinct age subgroups. The first subgroup comprised young breast cancer (YBC) patients, defined as women under the age of 40, while the second subgroup consisted of older breast cancer (OBC) patients. Our study aimed to characterize the molecular differences between these age-defined groups, providing insights into the underlying mechanisms of breast cancer in different age cohorts. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. Results 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. 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. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. Our analysis also revealed specific associations between genomic aberrations, organotropisms, and metastatic breast cancer. 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. Conclusion Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients. Figure 1. Genomic landscape of KM BRCA. (A) Overall characteristic of KM BRCA sample and clinical data. Clinical features of KM BRCA sample. (B) Genomic landscape of somatic mutations and copy number alterations of BRCA by age group. Figure 2. Genomic landscape of KM BRCA: Significantly mutated genes by age group in KM BRCA. Figure 3. Survival Curve Utilizing a curated Gene Set Developed by a Gradient-Boosting Multivariable Model (A) OS of platinum-based therapy treated KM with curated Gene set. (B) OS of platinum-based therapy treated MSK with curated Gene set. Citation Format: Kim Ju Won, LEE JIWON, Kyong Hwa Park, Seung Pil Jung, Jason Sa, SHIN SANG WON, An Jung Seok. Molecular and clinical disparities in breast cancer among East Asian populations abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-11.