| Title: |
Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers |
| Authors: |
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; Park, KH |
| Contributors: |
105544; Ahn, MS |
| Publication Year: |
2024 |
| Subject Terms: |
Adult; Age Factors; Aged; 80 and over; Asian People; Breast Neoplasms; Class I Phosphatidylinositol 3-Kinases; East Asian People; Female; GATA3 Transcription Factor; Humans; Middle Aged; Mutation; Receptor; ErbB-2; Breast cancer; Ethnic diversity; Genomic alterations; Molecular subtypes; Precision medicine |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
39334392 |
| Relation: |
J017417015; http://repository.ajou.ac.kr/handle/201003/33474; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438198 |
| DOI: |
10.1186/s12916-024-03638-y |
| Availability: |
http://repository.ajou.ac.kr/handle/201003/33474; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438198; https://doi.org/10.1186/s12916-024-03638-y |
| Accession Number: |
edsbas.AFFC12A8 |
| Database: |
BASE |