Triple-negative breast cancer: disease entity or title of convenience?
This Review outlines the understanding and management of triple-negative breast cancer (TNBC). TNBC shares morphological and genetic abnormalities with basal-like breast cancer (BLBC), a subgroup of breast cancer defined by gene-expression profiling. However, TNBC and BLBC tumors are heterogeneous and overlap is incomplete. Breast cancers found in BRCA1 mutation carriers are also frequently triple negative and basal like. TNBC and BLBC occur most frequently in young women, especially African Americans, and tend to exhibit aggressive, metastatic behavior. These tumors respond to conventional chemotherapy but relapse more frequently than hormone receptor-positive, luminal subtypes and have a worse prognosis. New systemic therapies are urgently needed as most patients with TNBC and/or BLBC relapse with distant metastases, and hormonal therapies and HER2-targeted agents are ineffective in this group of tumors. Poly (ADP-ribose) polymerase inhibitors, angiogenesis inhibitors, EGFR-targeted agents, and src kinase and mTOR inhibitors are among the therapeutic agents being actively investigated in clinical trials in patients with TNBC and/or BRCA1-associated tumors. Increased understanding of the genetic abnormalities involved in the pathogenesis of TNBC, BLBC and BRCA1-associated tumors is opening up new therapeutic possibilities for these hard-to-treat breast cancers.
Carey
Lisa
L
University of North Carolina, 170 Manning Drive, Chapel Hill, NC 27599-7305, USA.
Winer
Eric
E
Viale
Giuseppe
G
Cameron
David
D
Gianni
Luca
L
D000970:Antineoplastic Agents / Q000145:classification / Q000494:pharmacology / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000172:deficiency / Q000502:physiology; D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019090:Case Management; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D018734:Genes, erbB-2; D006801:Humans; D008940:Mitotic Index; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C492913:BRCA1 protein, human; C508053:ERBB2 protein, human