Triple negative breast cancer: molecular profiling and prognostic impact in adjuvant anthracycline-treated patients

Breast Cancer Res Treat. 2008 Sep;111(1):27-44. doi: 10.1007/s10549-007-9756-8. Epub 2007 Oct 6.


Background: We analysed the clinical features, distribution of basal markers, prevalence of oncogene amplification, and outcome of triple negative (TN) compared to those of non-TN cancers in a series of adjuvant-anthracycline treated breast cancer patients.

Methods: We examined the prognostic impact of the TN and BL phenotype in 245 breast cancer patients uniformly treated with adjuvant anthracycline-based chemotherapy following primary surgery, with regards to local relapse-free (LRFS), metastasis free (MFS), and breast cancer specific survival (BCSS). A comparative analysis of the clinicopathological characteristics, expression of basal markers (cytokeratins (Cks) 5/6, 14, 17, EGFR, and caveolin 1 and 2), MIB-1, p53 and topoisomerase II alpha, and prevalence of CCND1, MYC and TOP2A amplification in TN and non-TN breast tumours was performed.

Results: TN cancers were significantly associated with the expression of basal markers (all P < 0.0001). However 19.4% of TN tumours were negative for basal markers, whilst 7.3% of non-TN tumours expressed basal markers. TN phenotype was significantly associated with p53, MIB-1 and topoisomerase II alpha (all, P < 0.01) expression. No TN cancer harboured amplification of CCND1 or TOP2A. In univariate analysis, TN and BL phenotype were significantly associated with shorter MFS (both, P < 0.01) and BCSS (both, P < 0.005) but not LRFS.

Conclusions: Despite treatment with standard dose anthracycline-based chemotherapy, the clinical outcome of TN and BL cancers remains poor. Alternative chemotherapeutic regimens and/or novel therapeutic approaches are warranted. Although a significant phenotypic overlap exists between TN and basal-like tumours, the TN phenotype is not an ideal surrogate marker for basal-like breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracyclines / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Kaplan-Meier Estimate
  • Phenotype
  • Prognosis
  • Tissue Array Analysis


  • Anthracyclines
  • Antineoplastic Agents
  • Biomarkers, Tumor