Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype

Clin Cancer Res. 2008 Mar 1;14(5):1368-76. doi: 10.1158/1078-0432.CCR-07-1658.


Purpose: Basal-like breast cancer is associated with high grade, poor prognosis, and younger patient age. Clinically, a triple-negative phenotype definition [estrogen receptor, progesterone receptor, and human epidermal growth factor receptor (HER)-2, all negative] is commonly used to identify such cases. EGFR and cytokeratin 5/6 are readily available positive markers of basal-like breast cancer applicable to standard pathology specimens. This study directly compares the prognostic significance between three- and five-biomarker surrogate panels to define intrinsic breast cancer subtypes, using a large clinically annotated series of breast tumors.

Experimental design: Four thousand forty-six invasive breast cancers were assembled into tissue microarrays. All had staging, pathology, treatment, and outcome information; median follow-up was 12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the two immunohistochemical panels.

Results: Among 3,744 interpretable cases, 17% were basal using the triple-negative definition (10-year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests of multivariable Cox models including standard clinical variables show that the five-marker panel is significantly more prognostic than the three-marker panel. The poor prognosis of triple-negative phenotype is conferred almost entirely by those tumors positive for basal markers. Among triple-negative patients treated with adjuvant anthracycline-based chemotherapy, the additional positive basal markers identified a cohort of patients with significantly worse outcome.

Conclusions: The expanded surrogate immunopanel of estrogen receptor, progesterone receptor, human HER-2, EGFR, and cytokeratin 5/6 provides a more specific definition of basal-like breast cancer that better predicts breast cancer survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cohort Studies
  • ErbB Receptors / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • In Situ Hybridization, Fluorescence
  • Keratin-5 / metabolism*
  • Keratin-6 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*


  • Biomarkers, Tumor
  • Keratin-5
  • Keratin-6
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ErbB Receptors
  • Receptor, ErbB-2