Post-Mastectomy Radiation Therapy in HER-2 Positive Breast Cancer Patients: Analysis of the HERA Trial

Abstract Purpose Post-mastectomy radiation therapy (PMRT) improves recurrence rates and overall survival in breast cancer patients. However, it remains unclear whether these findings can be applied to HER-2 positive patients treated with trastuzumab. Methods and Materials The HERA trial is a phase III randomized clinical trial that established the efficacy of trastuzumab in HER-2 positive early stage breast cancer. The current study is a retrospective analysis of prospective data of 1633 trial patients treated with mastectomy and adjuvant trastuzumab. The primary objective of the study was to determine the effect of PMRT on loco-regional recurrence rates (LRR). Hazard ratios were estimated from Cox models and LRR curves were generated by the Kaplan-Meier method. Results Our analysis included 940 patients (57·6%) who received PMRT and 693 patients (42·4%) who did not. Patients in the PMRT group had worse prognostic disease characteristics. At a median follow up of 11 years, no significant difference in LRR was noted after PMRT in node negative (N0) patients (p-value = 0·96). Patients with 1-3 positive lymph nodes had a LRR-free survival of 97% in the PMRT group as compared to 90% in the no PMRT group (HR = 0·28, p-value = 0·004) and a non-significant improved overall survival (OS) after PMRT (HR = 0·63, p-value = 0·06). Conclusions PMRT delivery in HER-2 positive breast cancer patients with 1-3 positive lymph nodes decreases the risk of LRR. Although the magnitude of PMRT benefit is lower than historical studies, the current findings are in favor of PMRT for HER-2 positive breast cancer patients with 1-3 involved nodes. Future studies are needed to determine which HER-2 positive breast cancer patients benefit the most from PMRT.