title: Breast cancer genomics from microarrays to massively parallel sequencing: paradigms and new insights.
abstract: Rapid advancements in massively parallel sequencing methods have enabled the analysis of breast cancer genomes at an unprecedented resolution, which have revealed the remarkable heterogeneity of the disease. As a result, we now accept that despite originating in the breast, estrogen receptor (ER)-positive and ER-negative breast cancers are completely different diseases at the molecular level. It has become apparent that there are very few highly recurrently mutated genes such as TP53, PIK3CA, and GATA3, that no two breast cancers display an identical repertoire of somatic genetic alterations at base-pair resolution and that there might not be a single highly recurrently mutated gene that defines each of the "intrinsic" subtypes of breast cancer (ie, basal-like, HER2-enriched, luminal A, and luminal B). Breast cancer heterogeneity, however, extends beyond the diversity between tumors. There is burgeoning evidence to demonstrate that at least some primary breast cancers are composed of multiple, genetically diverse clones at diagnosis and that metastatic lesions may differ in their repertoire of somatic genetic alterations when compared with their respective primary tumors. Several biological phenomena may shape the reported intratumor genetic heterogeneity observed in breast cancers, including the different mutational processes and multiple types of genomic instability. Harnessing the emerging concepts of the diversity of breast cancer genomes and the phenomenon of intratumor genetic heterogeneity will be essential for the development of optimal methods for diagnosis, disease monitoring, and the matching of patients to the drugs that would benefit them the most.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (CKYN, AMS, BW, JSRF); Department of Medical Oncology, SIRIC, Institut Curie, Paris, France (FCB); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF).
authors.forename: Charlotte K Y
authors.initials: CK
authors.lastname: Ng
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (CKYN, AMS, BW, JSRF); Department of Medical Oncology, SIRIC, Institut Curie, Paris, France (FCB); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF).
authors.forename: Anne M
authors.initials: AM
authors.lastname: Schultheis
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (CKYN, AMS, BW, JSRF); Department of Medical Oncology, SIRIC, Institut Curie, Paris, France (FCB); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF).
authors.forename: Francois-Clement
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (CKYN, AMS, BW, JSRF); Department of Medical Oncology, SIRIC, Institut Curie, Paris, France (FCB); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). weigeltb@mskcc.org reisfilj@mskcc.org.
authors.forename: Britta
authors.initials: B
authors.lastname: Weigelt
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY (CKYN, AMS, BW, JSRF); Department of Medical Oncology, SIRIC, Institut Curie, Paris, France (FCB); Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY (JSRF). weigeltb@mskcc.org reisfilj@mskcc.org.
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D040081:Protein Array Analysis; D011960:Receptors, Estrogen / Q000032:analysis; D017422:Sequence Analysis, DNA
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D011960:Receptors, Estrogen