Trastuzumab Provides a Comparable Prognosis in Patients With HER2-Positive Breast Cancer to Those With HER2-Negative Breast Cancer: Post Hoc Analyses of a Randomized Controlled Trial of Post-Mastectomy Hypofractionated Radiotherapy

Abstract

Background and purpose: We investigated the locoregional effect of trastuzumab, and determined whether patients with human epidermal growth factor receptor (HER)2-positive breast cancer (BC) treated with trastuzumab could achieve comparable efficacy to that of patients with HER2-negative BC.

Materials and methods: This was post hoc analyses of data of 793 BC patients from a randomized controlled trial comparing post-mastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy. Survival rates were analyzed by the Kaplan-Meier method and compared by the log-rank test.

Results: Patients were classified into three groups: HER2-negative (HER2^-; n = 547), HER2-positve with trastuzumab (HER2⁺ + T; n = 136), and HER2-positive without trastuzumab (HER2⁺ - T; n = 110). The HER2⁺ + T group had significantly lower locoregional recurrence (LRR, 6.0% vs. 13.9%), distant metastasis (DM, 17.4% vs. 33.8%) and higher disease-free survival (DFS, 81.2% vs. 61.9%) at 5 years than that of the HER2⁺ - T group (P <.05). The HER2^- group had significantly lower LRR (6.8% vs. 13.9%), DM (22.4% vs. 33.8%) and higher DFS (76.1% vs. 61.9%) at 5 years than that of the HER2⁺ - T group (P <.05). The difference in LRR, DM and DFS at 5 years was not significant between the HER2⁺ + T group and HER2^- group (P >.05). Different annual LRR patterns was found among groups according to HR status.

Conclusion: Trastuzumab reduces LRR in patients with locally advanced HER2-positive BC who have received post-mastectomy radiotherapy. It provides comparable DFS to that with patients with HER2-negative BC.

Keywords: HER2; breast cancer; prognosis; radiotherapy; trastuzumab.

Figure 1

Trial profile. CFRT, conventional fractionated radiotherapy; HFRT, hypofractionated radiotherapy; HER2, human epidermal growth factor receptor 2.

Figure 2

Kaplan–Meier plots of locoregional recurrence (A), distant metastasis (B), disease-free survival (C), and overall survival (D) of patients grouped according to HER2 status and trastuzumab treatment. HER2⁻, HER2-negative; HER2⁺ + T, HER2-positive with trastuzumab; HER2⁺ − T, HER2-positive without trastuzumab.

Figure 3

Kaplan–Meier plots of locoregional recurrence (A, E), distant metastasis (B, F), disease-free survival (C, G), and overall survival (D, H) of HR-positive patients and HR-negative patients grouped according to HER2 status and trastuzumab treatment. HR⁻, hormonal receptor-negative; HR⁺, hormonal receptor-positive; HER2⁻, HER2-negative; HER2⁺ + T, HER2-positive with trastuzumab; HER2⁺ − T, HER2-positive without trastuzumab.

Figure 4

Annual hazard rates for locoregional recurrence of the entire group (A), HR-positive patients (B), and HR-negative patients (C) grouped according to HER2 status and trastuzumab treatment. HR⁻, hormonal receptor-negative; HR⁺, hormonal receptor-positive; HER2⁻, HER2-negative; HER2⁺ + T, HER2-positive with trastuzumab; HER2⁺ − T, HER2-positive without trastuzumab.