title: Clinical implications of the intrinsic molecular subtypes of breast cancer.
abstract: Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Electronic address: alprat@clinic.ub.es.
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Pineda
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Barbara
authors.initials: B
authors.lastname: Adamo
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Galván
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Aranzazu
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Lydia
authors.initials: L
authors.lastname: Gaba
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Díez
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Viladot
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Arance
authors.affiliation: Translational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain; Medical Oncology Department, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Muñoz
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification* / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020360:Neoadjuvant Therapy; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D064726:Triple Negative Breast Neoplasms / Q000145:classification / Q000188:drug therapy / Q000235:genetics
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Gene expression; PAM50; Subtype