In I-SPY2, multiple investigational treatment regimens are simultaneously and adaptively randomized against the shared control arm.4-10 The primary efficacy end point is pathologic complete response (pCR), defined as no invasive cancer in the breast and lymph nodes at the time of surgery.11,12 Patients with pCR have excellent long-term recurrence-free survival in all breast cancer subtypes, including HR+/HER2– cancers.12 Among patients with HR+HER2– early-stage breast cancer, only those with MammaPrint (MP) high-risk disease are eligible for the trial. The gene discussed is ERBB2; the disease is breast carcinoma.