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

• Published in: Radiotherapy and oncology 2023-07, Vol.184, p.109668-109668, Article 109668
• Main Authors: Saifi, Omran, Bachir, Bachir, Panoff, Joseph, Poortmans, Philip, Zeidan, Youssef H.
• Format: Article
• Language: English
• Subjects: Anti-HER2 targeted therapy; Complete pathological response; HER-2 positive breast cancer; Neoadjuvant; Primary systemic therapy; Radiation therapy
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2023.109668

•HER2 + breast cancer with complete nodal pathological response to primary systemic therapy derive no significant locoregional-control benefit from post-mastectomy radiotherapy.•Post-mastectomy radiotherapy improves locoregional control in ypN2-3 HER2 + breast cancer.•Clinical nodal stage at diagnosis and complete nodal pathological response to primary systemic therapy are the strongest predictors for locoregional recurrence in Her2 + breast cancer. 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.