Post-mastectomy radiation therapy in HER-2 positive breast cancer after primary systemic therapy: Pooled analysis of TRYPHAENA and NeoSphere trials

The role of post-mastectomy 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 complete nodal pathological response (ypN0) and 140 (45%) patients who did not. Patients with ypN0 had a 5-year LRRFS of 97% in both, the PMRT and no PMRT, groups (p = 0.94). Patients with ypN + had 5-year LRRFS of 89% in the PMRT group and 82% in the no PMRT group (p = 0.17). 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 ypN0 were significantly associated with loco-regional recurrence (LRR).Her2 + BC patients who achieve ypN0 after PST have excellent locoregional-control which supports de-escalation of PMRT. In contrast, patients with ypN2-3 disease derive significant benefit from PMRT. Clinical nodal stage at presentation and ypN0 status are significantly associated with LRR risk in Her2 + BC.