J Cancer 2018; 9(17):3168-3176. doi:10.7150/jca.24701

Research Paper

Significantly higher pathologic complete response (pCR) after the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy for HER2-positive breast cancer: Evidence from a meta-analysis of randomized controlled trials

Yu-tuan Wu1*, Zhou Xu1*, Bilal Arshad1*, Jiu-song Wu2*, Ke Zhang3*, He Wu1, Xin Li1, Hao Li1, Ying-cun Li2, Zhong-liang Wang3, Kai-nan Wu1, Ling-quan Kong1✉

1. Department of Endocrine and Breast Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
2. Department of General Surgery, Children's Hospital of Chongqing Medical University, Chongqing 400020, China
3. Department of Orthopedics, Children's Hospital of Chongqing Medical University, Chongqing 400020, China
*These authors have contributed equally to this work.

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Citation:
Wu Yt, Xu Z, Arshad B, Wu Js, Zhang K, Wu H, Li X, Li H, Li Yc, Wang Zl, Wu Kn, Kong Lq. Significantly higher pathologic complete response (pCR) after the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy for HER2-positive breast cancer: Evidence from a meta-analysis of randomized controlled trials. J Cancer 2018; 9(17):3168-3176. doi:10.7150/jca.24701. Available from http://www.jcancer.org/v09p3168.htm

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Abstract

Objectives: To investigate the effect of the concurrent use of trastuzumab and anthracycline-based neoadjuvant chemotherapy (NAC) for HER2-positive breast cancer in terms of pCR and cardiotoxicity.

Methods: We systematically searched Pubmed, Embase, Cochrane and SinoMed databases from inception until 1 July 2017 for relevant articles of randomized controlled studies. After identified all relevant studies that reported the concurrent use of trastuzumab and anthracycline-based NAC for HER2-positive locally advanced breast cancer, five eligible randomized studies were extracted relevant data and assessed for design and quality, and the meta-analysis was conducted to evaluate the risk ratio (RR) of pCR and other interesting outcomes, such as left ventricular ejection fraction (LVEF) decrease more than 10%, responses, recurrence free survival (RFS) and overall survival (OS).

Results: A total of five randomized controlled studies were included in the meta-analysis, including 232 HER2-positive locally advanced breast cancer patients received the concurrent use of trastuzumab and anthracycline-based NAC. The results showed that the pCR rate was significantly higher in the group received the concurrent use of trastuzumab and anthracycline-based NAC (48%) than that in the non-concurrent use of trastuzumab and anthracycline-based NAC group (26%) (RR: 1.76, 95%CI: 1.37-2.26, p<0.0001). Besides, higher rate of RFS (RR: 1.14, 95%CI: 1.03-1.26, p=0.009) was observed in the concurrent use of trastuzumab and anthracycline-based NAC group. No significant differences in LVEF decreased more than 10% (p=0.50) between both groups.

Conclusions: Our meta-analysis of randomized controlled studies showed that pCR rates are significantly higher in the concurrent use of trastuzumab and anthracycline-based NAC compared with the non-concurrent use of trastuzumab and anthracycline-based NAC for certain HER2-positive breast cancer, meanwhile without significant increase of the cardiotoxicity.

Keywords: Breast cancer, Neoadjuvant chemotherapy, Pathologic complete response (pCR), Human epidermal growth factor receptor 2 (HER2), Meta-analysis