Patients with HER2+ breast cancer can have high rates of response to neoadjuvant systemic therapy. However, it is still uncertain whether response predicts the benefit of post-mastectomy radiation. Here is a pooled analysis from two randomized phase 2 trials of neoadjuvant therapy for HER2+ breast cancer (TRYPHAENA and NeoSphere) that included 312 patients with cN+ disease who had mastectomy with or without radiation. Just over half these patients (55%) were ypN0 after neoadjuvant therapy, and their locoregional recurrence free survival (LRRFS) was 97% regardless of whether they received PMRT or not. Among ypN+ patients, those with ypN2-3 disease had a significant improvement in 5-year LRRFS with PMRT (92% v 75%). For those with ypN1 disease, the difference was not significant (85% v 89%). | Saifi, Radiother Oncol 2023