Review
Breast Cancer Molecular Stratification: From Intrinsic Subtypes to Integrative Clusters

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Breast carcinomas can be stratified into different entities based on clinical behavior, histologic features, and/or by biological properties. A classification of breast cancer should be based on underlying biology, which we know must be determined by the somatic genomic landscape of mutations. Moreover, because the latest generations of anticancer agents are founded on biological mechanisms, a detailed molecular stratification is a requirement for appropriate clinical management. Such stratification, based on genomic drivers, will be important for selecting patients for clinical trials. It will also facilitate the discovery of novel drivers, the study of tumor evolution, and the identification of mechanisms of treatment resistance. Assays for risk stratification have focused mainly on response prediction to existing treatment regimens. Molecular stratification based on gene expression profiling revealed that breast cancers could be classified in so-called intrinsic subtypes (luminal A and B, HER2-enriched, basal-like, and normal-like), which mostly corresponded to hormone receptor and HER2 status, and further stratified luminal tumors based on proliferation. The realization that a significant proportion of the gene expression landscape is determined by the somatic copy number alterations that drive expression in cis led to the newer classification of breast cancers into integrative clusters. This stratification of breast cancers into integrative clusters reveals prototypical patterns of single-nucleotide variants and is associated with distinct clinical courses and response to therapy.

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Breast Cancer Theme Issue

Supported by the Cancer Research UK Cambridge Institute, a Cancer Research UK Major Cancer Centre award, the Cambridge Experimental Cancer Medicine Centre, and the National Institute for Health Research Cambridge Biomedical Research Centre (C.C.); and The Norwegian Cancer Society, The Norwegian Research Council, The Health Region South-East of Norway, The K. G. Jebsen Foundation, and Radiumhospitalets legater (A.-L.B.-D. and H.G.R.).

Disclosures: None declared.

This article is part of a review series on next-generation breast cancer omics.