Elevated MYC signaling is associated with poor outcome. (A) Overall risk of breast cancer recurrence in patients with varying levels of MYC pathway activation. I-SPY TRIAL patients (n = 149) were divided into tertiles based on the relative expression of the genes in the MYC signature in their pretreatment biopsy samples. Differences in risk of disease recurrence between these groups were assessed using a Cox proportional hazards model and Wald’s test. (B) Correlation of MYC pathway activation with tumor burden after neoadjuvant chemotherapy. The MYC pathway activation tertile for the I-SPY TRIAL patients with gene expression data, and for which RCB (0-III; Symmans et al., 2007) was determined at the time of surgery (n = 133), was examined. The association between residual tumor burden and MYC pathway activation tertile was assessed using Fisher’s exact test. (C) Disease recurrence by MYC signature in RCB 0/I patients. (D) Disease recurrence by MYC signature in RCB II/III patients. (E) Multivariate analysis considering receptor status and MYC pathway activation as a continuous variable.