Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g: a randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer

Breast Cancer Res. 2014 May 23;16(3):R50. doi: 10.1186/bcr3661.


Introduction: The purpose of this study was to retrospectively explore the relationship between human epidermal growth factor receptor 2 (HER2) messenger RNA (mRNA) expression and efficacy in patients receiving trastuzumab plus docetaxel (HT) or trastuzumab emtansine (T-DM1).

Methods: Patients with HER2-positive, locally advanced or metastatic breast cancer (MBC) were randomly assigned to HT (n=70) or T-DM1 (n=67). HER2 status was assessed locally using immunohistochemistry or fluorescence in situ hybridization and confirmed retrospectively by central testing. HER2 mRNA expression was assessed using quantitative reverse transcriptase polymerase chain reaction.

Results: HER2 mRNA levels were obtained for 116/137 patients (HT=61; T-DM1=55). Median pretreatment HER2 mRNA was 8.9. The risk of disease progression in the overall population was lower with T-DM1 than with HT (hazard ratio (HR)=0.59; 95% confidence interval (CI) 0.36 to 0.97). This effect was more pronounced in patients with HER2 mRNA≥median (HR=0.39; 95% CI 0.18 to 0.85) versus <median (HR=0.85; 95% CI 0.44 to 1.67). In the T-DM1 arm, median progression-free survival (PFS) was not reached in patients with HER2 mRNA≥median and was 10.6 months in patients with HER2 mRNA<median. In the HT arm, PFS was 8.8 versus 9.8 months in patients with HER2 mRNA≥median versus<median, respectively. The effect of HER2 mRNA expression on objective response rates was less pronounced.

Conclusions: This exploratory analysis suggests that while overall, patients with HER2-positive MBC show improved PFS with T-DM1 relative to HT, the effect is enhanced in patients with tumor HER2 mRNA ≥ median.

Trial registration: NCT00679341.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Disease-Free Survival
  • Docetaxel
  • Female
  • Humans
  • Maytansine / analogs & derivatives*
  • Maytansine / therapeutic use
  • Middle Aged
  • RNA, Messenger / biosynthesis
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Retrospective Studies
  • Taxoids / therapeutic use*
  • Trastuzumab
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • RNA, Messenger
  • Taxoids
  • Maytansine
  • Docetaxel
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Ado-Trastuzumab Emtansine

Associated data