A human epidermal growth factor receptor 2 expression-based approach to neoadjuvant chemotherapy for operable breast cancer

Jpn J Clin Oncol. 2010 Jul;40(7):620-6. doi: 10.1093/jjco/hyq020. Epub 2010 Mar 18.

Abstract

Objective: We investigated the pathological effects of neoadjuvant chemotherapy based on the human epidermal growth factor receptor 2 in operable breast cancer.

Methods: This prospective clinical study was a pilot involving 63 female patients. Before surgery, patients with tumors overexpressing human epidermal growth factor receptor 2 received four cycles of 60 mg/m(2) anthracycline and 600 mg/m(2) cyclophosphamide every 3 weeks, whereas those whose tumors did not overexpress human epidermal growth factor receptor 2 received four cycles of 75 mg/m(2) docetaxel and 600 mg/m(2) cyclophosphamide every 3 weeks. A quasi-pathological complete response (i.e. absence of invasive tumor or only focal residual tumor cells) was the primary endpoint, with compliance and predictors for each regimen as secondary endpoints. If a quasi-pathological complete response was not achieved, then crossover to the alternative treatment was recommended.

Results: The quasi-pathological complete response rate was 36.5% (23 of 63) overall, 27.8% (5 of 18) for the anthracycline and cyclophosphamide regimen and 40.0% (18 of 45) for the docetaxel and cyclophosphamide regimen. Docetaxel and cyclophosphamide treatment induced a quasi-pathological complete response in most patients with triple-negative tumors (15 of 19). The relative dose intensity was 97.3% for the anthracycline and cyclophosphamide regimen and 96.6% for the docetaxel and cyclophosphamide regimen. Quasi-pathological complete response to the docetaxel and cyclophosphamide regimen was associated with low estrogen receptor and progesterone receptor expression and high MIB-1 and topoisomerase IIalpha expression, in univariate analyses, but only with low estrogen receptor expression in multivariate analysis.

Conclusions: Selecting neoadjuvant chemotherapy regimens on the basis of individual human epidermal growth factor receptor 2 status improved efficacy, with docetaxel and cyclophosphamide treatment showing particular promise in tumors with the potential to be highly malignant.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anthracyclines / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Cyclophosphamide / therapeutic use
  • Docetaxel
  • Female
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy*
  • Receptor, ErbB-2 / metabolism*
  • Taxoids / therapeutic use
  • Young Adult

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Cyclophosphamide
  • Receptor, ErbB-2