title: Targeting triple-negative breast cancer: optimising therapeutic outcomes.
abstract: BACKGROUND
  Triple-negative breast cancer (TNBC) is a distinct subset of breast cancer (BC) defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2. It is highly heterogeneous and displays overlapping characteristics with both basal-like and BC susceptibility gene 1 and 2 mutant BCs. This review evaluates the activity of emerging targeted agents in TNBC.
  
  
  METHODS
  A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with targeted and platinum-based therapies.
  
  
  CONCLUSIONS
  Our review identified TNBC studies of agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth, and survival pathways. Combining targeted agents with chemotherapy in TNBC produced only modest gains in progression-free survival, and had little impact on survival. Six TNBC subgroups have been identified and found to differentially respond to specific targeted agents. The use of biological preselection to guide therapy will improve therapeutic indices in target-bearing populations.
  
  
  CONCLUSIONS
  Ongoing clinical trials of targeted agents in unselected TNBC populations have yet to produce substantial improvements in outcomes, and advancements will depend on their development in target-selected populations.
authors.affiliation: Department of Medicine, University of British Columbia and; Department of Medical Oncology, BC Cancer Agency, Vancouver, Canada. Electronic address: kgelmon@bccancer.bc.ca.
authors.forename: K
authors.initials: K
authors.lastname: Gelmon
authors.affiliation: Medical Oncology, National Cancer Center Singapore and; Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Dent
authors.affiliation: Department of Oncology, University of Alberta and; Department of Medical Oncology, Cross Cancer Institute, Edmonton, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Mackey
authors.affiliation: Department of Medicine, Memorial University and; Cancer Care Program, Eastern Health, St John's, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Laing
authors.affiliation: Kaleidoscope Strategic, Toronto, Canada.
authors.forename: D
authors.initials: D
authors.lastname: McLeod
authors.affiliation: Department of Medicine, University of Toronto; Department of Medicine, Division of Medical Oncology/Hematology, Sunnybrook Health Sciences Centre, Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Verma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D058990:Molecular Targeted Therapy; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D058570:TOR Serine-Threonine Kinases; C499320:PARP1 protein, human; C546842:MTOR protein, human; C508053:ERBB2 protein, human