In the second prospective validation cohort, including 600 patients from a clinical trial cohort treated with adjuvant chemotherapy, proportional hazards models revealed a significant positive association between continuous TMEM doorway density score and early distant recurrence (P = 0.001) and locoregional plus distant recurrence (P = 0.00006) within 5 years of diagnosis in the subset of 297 patients with hormone receptor-positive, HER2-negative disease, but not in triple-negative or HER2-positive breast cancer. The gene discussed is ERBB2; the disease is breast cancer.