The Recurrence Score prognosticator fails to perform appropriately after adjustment for the cell cycle principal component variable. A. A ROC curve summarizing the performance of the 21-gene recurrence classifier in ER positive tumors in the NKI2 data set (n = 224 subjects) adjusted for either an intercept only (black line) or the cell cycle PC variable (grey line). The area under the curve (AUC) for each analysis is shown on the graph. The dotted line represents a ROC curve with an AUC of 0.5 (indicative of a low accuracy test). B/C. Kaplan-Meier plots for the recurrence score in the NKI2 data set for data adjusted for (B) intercept-only or (C) the cell cycle PC variable. Hazard ratios (HR) and p-values are from univariate proportional hazards analyses and represent the difference in hazards for poor versus good prognosis tumors. D. ROC curve for ER positive tumors in the KJX64/KJ125 data set (n = 147 subjects) adjusted for either an intercept only (black line) or the cell cycle PC variable (grey line).