Molecular subclasses in ER- breast cancer. (a) Complete linkage hierarchical clustering of 186 ER- breast tumors over 813 genes with negative kurtosis profiles. Five sample clusters were identified and characterized in terms of the patterns of over-expression and under-expression of four gene clusters related to cell cycle (CC; blue), immune response (IR; red), extracellular matrix (ECM; green), and steroid hormone response (SR; pink) functions. Panels show the distribution of the SSP subtype , the lymphocytic infiltration score, histologic grade, basal marker , and ERBB2+ amplifier subtype. Panel color codes: SSP (pink = HER2, brown = basal, dark green = normal, sky blue = luminal A, and blue = luminal B); LYM.INF (black = high, gray = low, and white = missing); GRADE (black = high, blue = intermediate, sky blue = low, and white = missing), BASAL.MARK. (black = high and white = low), ERBB2-AMP (black = high and white = low). The BASAL.MARK. profile represents an average over validated basal markers in , whereas the ERBB2-AMP profile was calculated as an average over three genes in the ERBB2 amplicon (ERBB2, STARD3, GRB7). (b) Kaplan-Meier curves for time to distant metastasis (years) and for the five subclasses identified in panel (a). (c) Partitioning around medoids clustering over the seven-gene prognostic immune response module. Panel color codes: purple = cluster over-expressing module, yellow = cluster under-expressing module, black = poor outcome samples, gray = good outcome samples, green = relative under-expression, and red = relative over-expression. (d) Kaplan-Meier curves for time to distant metastasis for the two groups identified in panel (c). Hazard ratio, 95% confidence interval, and log-rank test P values are shown. ER, estrogen receptor; SSP, single sample predictor.