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 basallike 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 assembledinto tissuemicroarrays. Allhad staging, pathology, treatment, andoutcomeinformation;median follow-up was12.5 years. Cox regression analyses and likelihood ratio tests compared the prognostic significance for breast cancer death-specific survival (BCSS) of the twoimmunohistochemicalpanels. Results: Among3,744interpretable cases,17%werebasalusing the triple-negativedefinition(10- year BCSS, 6 7%) and 9% were basal using the five-marker method (10-year BCSS, 62%). Likelihood ratio tests ofmultivariable Coxmodelsincluding standard clinical variables show that the fivemarker 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-negativepatients treatedwithadjuvant anthracycline-based chemotherapy, theadditionalpositive basalmarkersidentified 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
