Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial

Cancer. 2020 Mar 15;126(6):1175-1182. doi: 10.1002/cncr.32653. Epub 2019 Dec 18.


Background: Dose-dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)-positive disease.

Methods: This was a protocol-predefined secondary analysis of the randomized phase 3 Pan-European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node-positive or high-risk, node-negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5-fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2-positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse-free survival. In addition, HER2-positive patients and an equal number of HER2-negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow-up.

Results: There were 342 HER2-positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse-free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37-1.27; P = .231). Cardiac outcomes after 4 and 6 years of follow-up did not differ significantly between HER2-positive and HER2-negative patients or between the 2 treatment groups.

Conclusions: The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de-escalation strategies.

Trial registration: ClinicalTrials.gov NCT00798070.

Keywords: adjuvant chemotherapy; breast cancer; cardiotoxicity; dose-dense; human epidermal growth factor receptor 2 (HER2); trastuzumab.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant / methods
  • Confidence Intervals
  • Cyclophosphamide / administration & dosage
  • Disease-Free Survival
  • Docetaxel / administration & dosage
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Heart / drug effects
  • Humans
  • Middle Aged
  • Prospective Studies
  • Receptor, ErbB-2*
  • Trastuzumab / administration & dosage*
  • Trastuzumab / adverse effects
  • Young Adult


  • Antineoplastic Agents, Immunological
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Fluorouracil

Associated data

  • ClinicalTrials.gov/NCT00798070