Possible reasons why PREDICT underperformed in our study include weak external validity of randomised controlled trials,25 underestimation by PREDICT of survival of patients with HER2-positive breast cancer that fared particularly well in PANTHER,26 improved systemic therapy (chemotherapy and endocrine therapy) in PANTHER, overperformance of control arm,27 overestimation by PREDICT of competing causes of death in this high-risk cohort and a minority of patients that hadn't completed ten years of follow-up. The gene discussed is ERBB2; the disease is breast carcinoma.