Post-Mastectomy Radiation Therapy in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Patients: Analysis of the HERA Trial

Int J Radiat Oncol Biol Phys. 2020 Mar 1;106(3):503-510. doi: 10.1016/j.ijrobp.2019.10.022. Epub 2019 Oct 22.

Abstract

Purpose: Postmastectomy radiation therapy (PMRT) improves recurrence rates and overall survival in breast cancer patients. However, it remains unclear whether these findings can be applied to human epidermal growth factor receptor 2 (HER-2) positive patients treated with trastuzumab.

Methods and materials: The Herceptin Adjuvant (HERA) trial is a phase III randomized clinical trial that established the efficacy of trastuzumab in HER-2 positive early stage breast cancer. The present 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 = .96). Patients with 1 to 3 positive lymph nodes had a LRR-free survival of 97% in the PMRT group compared with 90% in the no PMRT group (hazard ratio = 0.28, P = .004) and a nonsignificant improved overall survival after PMRT (hazard ratio = 0.63, P = .06).

Conclusions: PMRT delivery in HER-2 positive breast cancer patients with 1 to 3 positive lymph nodes decreases the risk of LRR. Although the magnitude of PMRT benefit is lower than historic studies, the present findings are in favor of PMRT for HER-2 positive breast cancer patients with 1 to 3 involved nodes. Future studies are needed to determine which HER-2 positive breast cancer patients benefit the most from PMRT.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Agents, Immunological / therapeutic use
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Postoperative Period
  • Proportional Hazards Models
  • Receptor, ErbB-2*
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Retrospective Studies
  • Trastuzumab / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab