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Conservation of Breast Cancer Molecular Subtypes and Transcriptional Patterns of Tumor Progression Across Distinct Ethnic Populations

¹ National Cancer Centre/ ² Defence Medical and Environmental Research Institute, and ³ Department of Pathology, Singapore General Hospital, Republic of Singapore

Purpose: Breast cancers can display distinct clinical characteristics in different ethnic populations. Previous studies involving European and United States patients have shown that breast tumors can be divided by their gene expression profiles into distinct "molecular subtypes." In this report, we surveyed a series of invasive and preinvasive breast tumors from Asian-Chinese patients to investigate whether similar subtypes could also be observed in this ethnic group.

Experimental Design and Results: An analysis of expression profiles generated from 11 nonmalignant breast tissues, 17 ductal carcinomas in situ (DCIS) and 98 invasive carcinomas identified three broad molecular subtypes of breast [estrogen receptor (ER)+, ERBB2+ and ER–] in the Asian-Chinese population. These subtypes were highly similar to the "Luminal," "ERBB2+," and "Basal" molecular subtypes defined in previous studies, and the subtype-specific expression signatures were also observed in preinvasive DCIS tumors. By comparing the expression profiles of nonmalignant DCIS and invasive breast cancers for two subtypes (ER+ and ERBB2+), we identified several genes that were regulated in both a common and subtype-specific manner during the normal/DCIS and DCIS/invasive carcinoma transitions. Several of these genes were validated by comparison with another recently published similar, but not identical, study.

Conclusions: Our results suggest that molecularly similar subtypes of breast cancer are indeed broadly conserved between Asian and Caucasian patients, and that these subtypes are already present at the preinvasive stage of carcinogenesis. To our knowledge, this study is among the first to directly compare the expression profiles of breast tumors across two different ethnic populations.

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