title: Molecular alterations in triple-negative breast cancer-the road to new treatment strategies.
abstract: Triple-negative breast cancer is a heterogeneous disease and specific therapies have not been available for a long time. Therefore, conventional chemotherapy is still considered the clinical state of the art. Different subgroups of triple-negative breast cancer have been identified on the basis of protein expression, mRNA signatures, and genomic alterations. Important elements of triple-negative breast cancer biology include high proliferative activity, an increased immunological infiltrate, a basal-like and a mesenchymal phenotype, and deficiency in homologous recombination, which is in part associated with loss of BRCA1 or BRCA2 function. A minority of triple-negative tumours express luminal markers, such as androgen receptors, and have a lower proliferative activity. These biological subgroups are overlapping and currently cannot be combined into a unified model of triple-negative breast cancer biology. Nevertheless, the molecular analysis of this disease has identified potential options for targeted therapeutic intervention. This has led to promising clinical strategies, including modified chemotherapy approaches targeting the DNA damage response, angiogenesis inhibitors, immune checkpoint inhibitors, or even anti-androgens, all of which are being evaluated in phase 1-3 clinical studies. This Series paper focuses on the most relevant clinical questions, summarises the results of recent clinical trials, and gives an overview of ongoing studies and trial concepts that will lead to a more refined therapy for this tumour type.
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Germany; German Cancer Consortium (DKTK), Partner Site Berlin, Germany. Electronic address: carsten.denkert@charite.de.
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.affiliation: University Hospital Schleswig-Holstein, Campus Lübeck, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Liedtke
authors.affiliation: The Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research and Breast Cancer Now Research Unit, King's College, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tutt
authors.affiliation: German Breast Group, Neu-Isenburg, Germany.
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D024682:BRCA2 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics / Q000379:methods; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation; D020360:Neoadjuvant Therapy / Q000379:methods; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases