Triple negative breast cancer: from molecular portrait to therapeutic intervention.
Triple negative breast cancer is a subtype of breast cancer that lacks expression of an estrogen receptor (ER), a progesterone receptor (PR), and HER2. It is characterized by its unique molecular profile, aggressive behavior, and distinct pattern of metastasis. Epidemiological studies show a high prevalence of triple negative breast cancer among younger women and those of African descent. Although sensitive to chemotherapy, early relapse is common, and a predilection for visceral metastasis, including brain metastasis, has been described. Gene-expression profiling approaches demonstrated that triple negative breast cancer is a heterogeneous group of diseases composed of different, molecularly distinct subtypes. Although not synonymous, the majority of triple negative breast cancers carry the "basal-like" molecular profile on gene-expression arrays. However, several studies have shown that triple negative breast cancer includes tumors with a non-basal expression profile and, in particular, the "normal-breast," the "multiple marker negative," and the recently identified "claudin-negative" subtypes. Target-based agents, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and poly-ADP-ribose polymerase (PARP) inhibitors, are currently in clinical trials and hold promise in the treatment of this aggressive disease.
Pharmacogenomic Laboratory, CROM - Oncological Research Center Mercogliano, 83013 Avellino, Italy.
Pietro
P
Carotenuto
Cristin
C
Roma
Anna Maria
AM
Rachiglio
Gerardo
G
Botti
Amelia
A
D'Alessio
Nicola
N
Normanno
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D011960:Receptors, Estrogen / Q000172:deficiency* / Q000235:genetics; D011980:Receptors, Progesterone / Q000172:deficiency* / Q000235:genetics
D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone