[Identification of basal-like carcinomas in clinical practice: "triple zero/BRCA1-like" carcinomas]

Bull Cancer. 2010 Mar;97(3):357-63. doi: 10.1684/bdc.2010.1062.
[Article in French]

Abstract

Basal-like carcinomas represent 10 to 15% of invasive breast carcinomas and have been identified from gene expression studies. Morphologically, these tumors are undifferentiated histopronostic grade 3 carcinomas, identified in clinical practice according to their immunophenotype "triple zero" (estrogen, progesterone and ERBB2 negative) associated with the high molecular weight cytokeratins 5/6/14 and/or EGFR expression. At the molecular level, these tumors harbour nearly 100% P53 mutations, a high rate of PTEN mutations with an AKT pathway's activation and numerous chromosomal alterations such as gains and losses. They share a high degree of similarity at the morphological, phenotypical and molecular level with BRCA1 tumors that justify the proposal of a different name such as "triple zero/BRCA1 like" carcinomas for sporadic basal-like carcinomas. Indeed, the current "basal-like" name could suggest a myoepithelial cellular origin of such lesions. Furthermore, tumors with such a basal-like immunophenotype constitute a heterogeneous group of tumors encompassing good prognosis tumors such as adenoid cystic and juvenile secretory carcinomas. There is an urgent need for more specific therapies for basal-like/triple zero/BRCA1-like tumors. Therapeutic progresses rely on a better understanding of the molecular alterations that occur in these tumors and the BRCA1 tumors. Indeed, recent clinical trials with PARP inhibitors for basal-like/BRCA1 like tumors should improve the prognosis of these patients and are a direct benefit of a better understanding of the molecular biology of these tumors.

Publication types

  • English Abstract

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Biomarkers, Tumor
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Female
  • Gene Expression Profiling / methods*
  • Gene Silencing
  • Genes, BRCA1*
  • Genes, p53 / genetics
  • Humans
  • Mutation / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Phenotype
  • Prognosis
  • Terminology as Topic

Substances

  • BRCA1 Protein
  • Biomarkers, Tumor
  • Neoplasm Proteins