Molecular insights on basal-like breast cancer

Breast Cancer Res Treat. 2012 Jul;134(1):21-30. doi: 10.1007/s10549-011-1934-z. Epub 2012 Jan 11.

Abstract

Molecular classification of breast cancer (BC) identified diverse subgroups that encompass distinct biological behavior and clinical implications, in particular in relation to prognosis, spread, and incidence of recurrence. Basal-like breast cancers (BLBC) compose up to 15% of BC and are characterized by lack of estrogen receptor (ER), progesterone receptor (PR), and HER-2 amplification with expression of basal cytokeratins 5/6, 14, 17, epidermal growth factor receptor (EGFR), and/or c-KIT. There is an overlap in definition between triple-negative BC and BLBC due to the triple-negative profile of BLBC. Also, most BRCA1-associated BCs are BLBC, triple negative, and express basal cytokeratins (5/6, 14, 17) and EGFR. There is a link between sporadic BLBC (occurring in women without germline BRCA1 mutations) with dysfunction of the BRCA1 pathway. Despite the molecular and clinical similarities, these subtypes respond differently to neoadjuvant therapy. BLBCs are associated with an aggressive phenotype, high histological grade, poor clinical behavior, and high rates of recurrences and/or metastasis. Their molecular features render these tumors especially refractory to anti-hormonal-based therapies and the overall prognosis of this subset remains poor. In this article, the molecular profile, genomic, and epigenetic characteristics as well as BRCA1 pathway dysfunction, clinicopathological behavior, and therapeutic options in BLBC are presented, with emphasis on the discordant findings in current literature.

Publication types

  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / classification
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Female
  • Gene Amplification
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Keratins, Hair-Specific
  • Keratins, Type I / metabolism
  • Keratins, Type II / metabolism
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism
  • Receptors, Steroid / metabolism

Substances

  • Keratins, Hair-Specific
  • Keratins, Type I
  • Keratins, Type II
  • Receptors, Steroid
  • ERBB2 protein, human
  • Receptor, ErbB-2