title: Dissecting the heterogeneity of triple-negative breast cancer.
abstract: Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers. It is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. TNBC is associated with a significantly higher probability of relapse and poorer overall survival in the first few years after diagnosis when compared with other breast cancer subtypes. This is observed despite its usual high sensitivity to chemotherapy. In the advanced setting, responses observed with chemotherapy lack durability. Early-stage clinical studies suggested impressive potential when a poly (ADP-ribose) polymerase (PARP) inhibitor is given for the treatment of advanced TNBC with BRCA gene dysfunction. The molecular complexity of TNBC has led to proposed subclassifications, which will be of great value for the development of targeted therapies. In this review, we discuss the biology of TNBC at the pathologic and the molecular levels. We also elaborate on the role of systemic therapies and the results of the first phase III clinical trial evaluating the addition of iniparib, a novel investigational anticancer agent that does not possess characteristics typical of the PARP inhibitor class, in combination with chemotherapy in advanced TNBC.
authors.affiliation: Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Otto
authors.initials: O
authors.lastname: Metzger-Filho
authors.forename: Andrew
authors.initials: A
authors.lastname: Tutt
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.forename: Kamal S
authors.initials: KS
authors.lastname: Saini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Sherene
authors.initials: S
authors.lastname: Loi
authors.forename: Ian
authors.initials: I
authors.lastname: Bradbury
authors.forename: Judith M
authors.initials: JM
authors.lastname: Bliss
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Azim
authors.forename: Paul
authors.initials: P
authors.lastname: Ellis
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart-Gebhart
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000145:classification / Q000453:epidemiology / Q000235:genetics / Q000473:pathology / Q000628:therapy; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D058990:Molecular Targeted Therapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human