Breast Cancer Research and Treatment

, Volume 173, Issue 1, pp 1–9 | Cite as

Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis

  • Y. ShenEmail author
  • T. Fujii
  • N. T. Ueno
  • D. Tripathy
  • N. Fu
  • H. Zhou
  • J. Ning
  • L. Xiao



Trastuzumab (H) with chemotherapy benefits patients with HER2+ breast cancer (BC); however, we lack head-to-head pairwise assessment of survival or cardiotoxicity for specific combinations. We sought to identify optimal combinations.


We searched PubMed, updated October 2017, using keywords “Breast Neoplasms/drug therapy,” “Trastuzumab,” and “Clinical Trial” and searched Cochrane Library. Our search included randomized trials of adjuvant H plus chemotherapy for early-stage HER2+ BC, and excluding trials of neoadjuvant therapy or without data to obtain hazard ratios (HRs) for outcomes. Following PRISMA guidelines, one investigator did initial search; two others independently confirmed and extracted information; and consensus with another investigator resolved disagreements. Before gathering data, we set outcomes of overall survival (OS), event-free survival (EFS), and severe cardiac adverse events (SCAEs). Analyzing 6 trials and 13,621 patients, we made direct and indirect comparisons using network meta-analysis on HR for OS or EFS and on odds ratio (OR) for SCAE; ranked therapy was done based on outcomes using p scores.


Compared with anthracycline-cyclophosphamide with taxane (ACT), ACT with concurrent H (ACT+H) showed best OS (HR 0.63, 95% confidence interval [CI] 0.55, 0.72), followed by taxane and carboplatin (TC) with concurrent H (TC+H) (HR 0.77, 95% CI 0.59, 1) and ACT with sequential H (ACT-H) (HR 0.85, 95% CI 0.68, 1.05). Pairwise comparisons showed statistically significant OS benefit for ACT+H over others; similar results for EFS. TC+H showed statistically significant lower SCAE risk compared to ACT+H (OR 0.13, 95% CI 0.03, 0.61).


Concurrent H with ACT or TC showed most clinical benefit for early-stage HER2+ BC; TC+H had lowest cardiotoxicity.


Anthracycline Carboplatin Cardiotoxicity Cyclophosphamide Overall survival Taxane 



LeeAnn Chastain, BA, of the Department of Biostatistics at The University of Texas MD Anderson Cancer Center provided scientific editing services.

Author Contributions

YS and LX have full access to all of the data in the study collected from literature, and take responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: YS, TF, NTU, and LX. Acquisition, analysis, or interpretation of data: YS, LX, TF, NF, JN, HZ, NTU, and DT. Drafting of the manuscript: YS, LX, and TF. Critical revision of the manuscript for important intellectual content: YS, LX, TF, NTU, DT, JN, and NF. Statistical analysis: LX, HZ, JN, and YS. Obtained funding: YS, JN, and NTU. Administrative, technical, or material support: NF, YS, and LX. Study supervision: YS and NTU.


This study was partially supported by MD Anderson Cancer Center Support Grant from NCI (Grant CA016672), which supports the Biostatistics Share Resource.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

10549_2018_4969_MOESM1_ESM.doc (393 kb)
Supplementary material 1 (DOC 393 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of BiostatisticsThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Section of Translational Breast Cancer, Department of Breast Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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