Postmastectomy Radiation in HER-2 Positive Breast Cancer after Neoadjuvant Therapy: Secondary Analysis of Two Randomized Trials

The role of postmastectomy radiation therapy (PMRT) following primary systemic therapy (PST) in HER-2 positive breast cancer (Her2+BC) remains poorly understood. The current study evaluates PMRT based on the pathological response to PST in Her2+BC.TRYPHAENA and NeoSphere are randomized phase II trials that investigated PST for Her2+BC. Our study is a pooled analysis of both trials, including 312 node-positive patients treated with HER-2 targeted PST followed by mastectomy with or without PMRT. The primary endpoint is loco-regional recurrence-free survival (LRRFS).Our analysis included 172 (55%) patients who achieved nodal pCR and 140 (45%) patients who did not. Patients with nodal pCR had a 5-year LRRFS of 97% with PMRT delivered in 98 patients (57%). Patients without nodal pCR had a 5-year LRRFS of 87% with PMRT delivered in 93 patients (66%). Patients with ypN1 (n = 62) disease who received PMRT (n = 40) had a 5-year LRRFS of 85% as compared to 89% in those who did not (n = 22); (p = 0.60). A significant LRRFS difference was noted in patients with ypN2-3 (n = 78) disease who received PMRT (n = 53) compared to those who did not (n = 25) (5-year LRRFS 92% vs. 75%; p = 0.019). On multivariate analysis, clinical nodal disease at diagnosis and nodal pCR were significantly associated with loco-regional recurrence (LRR).Her2+BC patients who achieve nodal pCR after PST have excellent loco-regional control which supports de-escalation of PMRT.