Addition of zoledronic acid to neoadjuvant chemotherapy does not enhance tumor response in patients with HER2-negative stage II/III breast cancer: the NEOZOTAC trial (BOOG 2010-01)

Ann Oncol. 2014 May;25(5):998-1004. doi: 10.1093/annonc/mdu102. Epub 2014 Feb 27.

Abstract

Background: The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before.

Patients and methods: NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4 mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status.

Results: Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms.

Conclusions: Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.

Keywords: bisphosphonates; menopausal status; neoadjuvant chemotherapy; zoledronic acid.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Diphosphonates / administration & dosage
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Humans
  • Imidazoles / administration & dosage
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism*
  • Taxoids / administration & dosage
  • Treatment Outcome
  • Zoledronic Acid

Substances

  • Diphosphonates
  • Imidazoles
  • Taxoids
  • Docetaxel
  • Zoledronic Acid
  • Doxorubicin
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2