Impact of hormone receptor status on the efficacy of HER2-targeted treatment

Abstract

The introduction of human epidermal growth factor receptor 2 (HER2)-targeted drugs into routine clinical practice has a dramatic effect on the outlook for patients with HER2- positive breast cancer (BC). However, the association between efficacy of HER2-targeted therapy and hormone receptor (HR) status is still unclear. Here we conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue in both neoadjuvant and adjuvant settings. PubMed and EMBASE were searched from inception to October 2017 for studies involving trastuzumab, lapatinib, pertuzumab, trastuzumab emtansine and neratinib. Efficacy endpoints were pathological complete response (pCR) for neoadjuvant therapy and disease-free survival (DFS) for adjuvant therapy. In neoadjuvant setting, pCR was reported in 7 trials with 2868 subjects. Hormone receptor (HR)-negative women derived substantially greater benefit from HER2-targeted agents than did HR-positive patients (odds ratio (OR), 2.34; 95% confidence interval (CI), 1.99-2.75). Additionally, the impact of HR status on pCR was independent of anti-HER2 agents. In adjuvant setting, DFS was investigated in 7 studies with 12, 768 patients. HR-positive patients benefit more from anti-HER2 treatment than did HR-negative subjects (OR, 0.81; 95% CI, 0.74-0.89). Moreover, patients who did not receive any endocrine or anti-HER2 neoadjuvant treatment showed similar outcome but with a smaller effect (OR, 0.88; 95% CI, 0.78-0.99). In summary, compared with HER2-positive/HR-negative subjects, HER2-positive/HR-positive patients achieved greater benefit from HER2-targeted treatment although the efficacy from neoadjuvant therapy was relatively poor.