HER2 positivity is not associated with adverse prognosis in high-risk estrogen receptor-positive early breast cancer patients treated with chemotherapy and trastuzumab

Abstract

Co-expression of human epidermal growth factor receptor-2 (HER2) and hormone receptor (HR) predicted worse prognosis in early breast cancer before trastuzumab was developed. We aimed to investigate whether HER2 positivity was still associated with worse outcome in high-risk estrogen receptor (ER) positive patients treated with trastuzumab and chemotherapy. In the present study, 227 ER+/HER2+ patients treated with trastuzumab and chemotherapy (HER2-pos-T group) and 1097 ER+/HER2-patients treated with chemotherapy alone (HER2-neg group) during 2009 and 2015 were retrospectively enrolled for the comparison of disease-free survival (DFS) and overall survival (OS). At a median follow-up of 59 months, 174 DFS events and 69 deaths were observed. The estimated 5-year DFS rate was 94.2% in the HER2-pos-T group and 87.4% in the HER2-neg group (Log-rank P = 0.014). HER2-pos-T group was associated with significantly better DFS in multivariate analysis (HR 0.38, 95% CI: 0.22-0.67, Log-rank P = 0.001). The estimated 5-year OS rates for the two groups were 97.2% and 95.7%, respectively (Log-rank P = 0.183). In multivariable analysis, patients in the HER2-pos-T group had significantly better OS compared with those in the HER2-neg group (HR 0.40, 95% CI: 0.17-0.95, Log-rank P = 0.037). We concluded that high-risk ER+/HER2+ breast cancer patients treated with chemotherapy and trastuzumab had superior prognosis compared with ER+/HER2-patients. Therefore, HER2 positivity itself may not be considered as an unfavorable factor for ER + patients in the era of trastuzumab.

Keywords: Breast neoplasms; ErbB-2; Estrogen; Prognosis; Receptor; Receptors; Trastuzumab.

Fig. 1

Flowchart of the 1306 patients included in the study. Abbreviations: DCIS, ductal carcinoma in situ; ER, estrogen receptor; Tx, primary tumor cannot be assessed; Nx, lymph nodes cannot be assessed; HER2, human epidermal growth factor receptor 2.

Fig. 2

Survival analysis in the whole population. (A) The estimated 5-year DFS rate was 87.4% for HER2-neg patients and 94.2% for HER2-pos patients treated with trastuzumab. HER2-pos-T was associated with significantly better DFS both in univariate analysis (Log-rank P = 0.014) and multivariate analysis (HR 0.38, 95% CI: 0.22–0.67, Log-rank P = 0.001). (B) The estimated 5-year OS rate was 95.7% in the HER2-neg group and 97.2% in the HER2-pos-T group (Log-rank P = 0.183). HER2-pos-T was associated with significantly better OS (HR 0.40, 95% CI: 0.17–0.95, Log-rank P = 0.037) after adjusting menstrual status, histological type, tumor size, ALN status, histological grade, ER, and PR. (C) Estimated and smoothed annual incidence of DFS events in the HER2-neg group and HER2-pos-T group ∗. (D) Estimated and smoothed annual incidence of OS events in the HER2-neg group and HER2-pos-T group ∗. ∗ In C/D panels, dots and triangles represent estimated annual incidence of DFS/OS events in the HER2-neg group and HER2-pos-T group, respectively.