Switching to T-DM1 remains justified in patients with HER2-negative residual invasive breast cancer after neoadjuvant therapy

Reductions in HER2-protein IHC intensity and HER2-gene amplification in residual invasive breast cancer following neoadjuvant therapy for HER2-positive breast cancer have been described and are associated with worse outcomes. T-DM1 requires initial binding to HER2 for activity, so concerns have been raised regarding T-DM1 activity when changes are sufficient to classify residual disease as HER2-negative. The KATHERINE trial assessed HER2 status of residual disease from 845 patients with HER2-positive status on pretherapy biopsies, of which 70 were negative on retesting. With 8 years of median follow-up, 7-year IDFS was 60.3 % with trastuzumab compared to 95.2 % with T-DM1, consistent with clinically meaningful benefit from T-DM1 in these 70 patients.