Abstract
Breast cancer (BC) in the Asia Pacific regions is enriched in younger patients and rapidly rising in incidence yet its molecular bases remain poorly characterized. Here we analyze the whole exomes and transcriptomes of 187 primary tumors from a Korean BC cohort (SMC) enriched in pre-menopausal patients and perform systematic comparison with a primarily Caucasian and post-menopausal BC cohort (TCGA). SMC harbors higher proportions of HER2+ and Luminal B subtypes, lower proportion of Luminal A with decreased ESR1 expression compared to TCGA. We also observe increased mutation prevalence affecting BRCA1, BRCA2, and TP53 in SMC with an enrichment of a mutation signature linked to homologous recombination repair deficiency in TNBC. Finally, virtual microdissection and multivariate analyses reveal that Korean BC status is independently associated with increased TIL and decreased TGF-β signaling expression signatures, suggesting that younger Asian BCs harbor more immune-active microenvironment than western BCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Asian People
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BRCA1 Protein / genetics
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BRCA1 Protein / immunology
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BRCA2 Protein / genetics
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BRCA2 Protein / immunology
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Biomarkers, Tumor / genetics*
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Biomarkers, Tumor / immunology
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Breast Neoplasms / ethnology
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Breast Neoplasms / genetics*
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Breast Neoplasms / immunology
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Breast Neoplasms / pathology
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Carcinoma, Ductal / ethnology
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Carcinoma, Ductal / genetics*
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Carcinoma, Ductal / immunology
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Carcinoma, Ductal / pathology
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Carcinoma, Lobular / ethnology
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Carcinoma, Lobular / genetics*
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Carcinoma, Lobular / immunology
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Carcinoma, Lobular / pathology
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Cohort Studies
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / immunology
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Exome Sequencing
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Female
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Humans
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Middle Aged
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Neoplasm Staging
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Postmenopause
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Premenopause
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Receptor, ErbB-2 / genetics
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Receptor, ErbB-2 / immunology
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Transcriptome*
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / immunology
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Tumor Microenvironment / genetics
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / immunology
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White People
Substances
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BRCA1 Protein
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BRCA1 protein, human
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BRCA2 Protein
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BRCA2 protein, human
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Biomarkers, Tumor
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ESR1 protein, human
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Estrogen Receptor alpha
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TP53 protein, human
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Transforming Growth Factor beta
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Tumor Suppressor Protein p53
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ERBB2 protein, human
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Receptor, ErbB-2