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Open Access Highly Accessed Research article

Effect and safety of dual anti-human epidermal growth factor receptor 2 therapy compared to monotherapy in patients with human epidermal growth factor receptor 2-positive breast cancer: a systematic review

Xiao Zhang1, Xin-Ji Zhang1, Tian-Yi Zhang1, Fei-Fei Yu1, Xin Wei2, Ye-Sheng Li3 and Jia He1*

Author Affiliations

1 Department of Health Statistics, Second Military Medical University, Shanghai, China

2 Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

3 Department of Special Treatment, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai, China

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BMC Cancer 2014, 14:625  doi:10.1186/1471-2407-14-625

Published: 28 August 2014

Abstract

Background

Dual anti-human epidermal growth factor receptor 2 (HER2) therapies have been shown to improve outcomes of HER2-positive breast cancer patients. We undertook a systematic review to compare treatment outcomes for patients who received single or combined anti-HER2 therapies.

Methods

We identified randomized control trials that compared dual anti-HER2 therapy and anti-HER2 monotherapy in patients with HER2-positive breast cancer. Outcomes included pathologic complete response (pCR), overall survival (OS), progression-free survival (PFS), and adverse events. Included in the analysis were seven trials that recruited 2,609 patients.

Results

In the neoadjuvant setting, the pooled pCR rate in the dual anti-HER2 therapy and monotherapy groups in combination with chemotherapy was 54.8% and 36%, respectively. This difference was statistically significant (relative risk, 1.56; 95% confidence interval (CI), 1.23–1.97; p < 0.001). In the metastatic setting, dual anti-HER2 therapy demonstrated significant benefits in both PFS (hazard ratio (HR), 0.71; 95% CI, 0.62–0.81; p < 0.001) and OS (HR, 0.68; 95% CI, 0.57–0.82; p < 0.001). Subgroup analyses indicated that the addition of chemotherapy to dual anti-HER2 therapy could greatly improve pCR in the neoadjuvant settings. However, in the metastatic setting, similar PFS and OS were found in patients receiving dual anti-HER2 therapy with or without chemotherapy. Dual anti-HER2 therapy was associated with more frequent adverse events than monotherapy, but no statistical differences were observed in cardiac toxicity.

Conclusions

This systematic review provides a summary of all the data currently available, and confirms the benefits and risks of dual anti-HER2 therapy for HER2-positive breast cancer.

Keywords:
anti-HER2 therapy; HER2-positive breast cancer; Systematic review