title: Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
abstract: Chemotherapy is the primary established systemic treatment for patients with triple-negative breast cancer (TNBC) in both the early and advanced-stages of the disease. The lack of targeted therapies and the poor prognosis of patients with TNBC have fostered a major effort to discover actionable molecular targets to treat patients with these tumours. Massively parallel sequencing and other 'omics' technologies have revealed an unexpected level of heterogeneity of TNBCs and have led to the identification of potentially actionable molecular features in some TNBCs, such as germline BRCA1/2 mutations or 'BRCAness', the presence of the androgen receptor, and several rare genomic alterations. Whether these alterations are molecular 'drivers', however, has not been clearly established. A subgroup of TNBCs shows a high degree of tumour-infiltrating lymphocytes that also correlates with a lower risk of disease relapse and a higher likelihood of benefit from chemotherapy. Proof-of-principle studies with immune-checkpoint inhibitors in advanced-stage TNBC have yielded promising results, indicating the potential benefit of immunotherapy for patients with TNBC. In this Review, we discuss the most relevant molecular findings in TNBC from the past decade and the most promising therapeutic opportunities derived from these data.
authors.affiliation: Department of Medical Oncology, IRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132 Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Bianchini
authors.affiliation: Department of Medicine Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC Building 4918-A, Nashville, Tennessee 37232, USA.|Department of Cancer Biology, Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC Building 4918-A, Nashville, Tennessee 37232, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Balko
authors.affiliation: Department of Medicine Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC Building 4918-A, Nashville, Tennessee 37232, USA.
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Mayer
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC Building 4918-A, Nashville, Tennessee 37232, USA.
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Sanders
authors.affiliation: Department of Medical Oncology, IRCCS Ospedale San Raffaele, Via Olgettina 60, Milan, 20132 Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D024682:BRCA2 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000378:metabolism; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007107:Immune System / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000628:therapy*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D000726:Androgen Antagonists; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; D020928:Mitogen-Activated Protein Kinases