TRAIN-2

TRAIN-2, trial NCT01996267 run by the Dutch Breast Cancer Research Group and published in the Lancet Oncology in 2018, randomised 438 patients with stage II or III HER2-positive breast cancer to nine cycles of carboplatin and paclitaxel with trastuzumab and pertuzumab, or to three cycles of fluorouracil, epirubicin and cyclophosphamide with the antibodies followed by six cycles of the same carboplatin-paclitaxel regimen. Pathological complete response in breast and axilla was 67 percent without the anthracycline and 68 percent with it, and the anthracycline arm had more febrile neutropenia and falls in left ventricular ejection fraction. Three-year event-free survival was 93.5 percent without and 92.7 percent with the anthracycline in the 2021 follow-up, and anthracycline-free dual-blockade regimens became the usual neoadjuvant approach in Europe. Whether a shorter or de-escalated regimen matches nine cycles is the question that followed.