title: 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).
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.
  
  
  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.
authors.affiliation: Department of Clinical Oncology.
authors.forename: A
authors.initials: A
authors.lastname: Charehbili
authors.forename: S
authors.initials: S
authors.lastname: van de Ven
authors.forename: V T H B M
authors.initials: VT
authors.lastname: Smit
authors.forename: E
authors.initials: E
authors.lastname: Meershoek-Klein Kranenbarg
authors.forename: N A T
authors.initials: NA
authors.lastname: Hamdy
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.forename: J B
authors.initials: JB
authors.lastname: Heijns
authors.forename: L J C
authors.initials: LJ
authors.lastname: van Warmerdam
authors.forename: L
authors.initials: L
authors.lastname: Kessels
authors.forename: M
authors.initials: M
authors.lastname: Dercksen
authors.forename: M J
authors.initials: MJ
authors.lastname: Pepels
authors.forename: E
authors.initials: E
authors.lastname: Maartense
authors.forename: H W M
authors.initials: HW
authors.lastname: van Laarhoven
authors.forename: B
authors.initials: B
authors.lastname: Vriens
authors.forename: M N
authors.initials: MN
authors.lastname: Wasser
authors.forename: A E
authors.initials: AE
authors.lastname: van Leeuwen-Stok
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: J W R
authors.initials: JW
authors.lastname: Nortier
authors.forename: J R
authors.initials: JR
authors.lastname: Kroep
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D003520:Cyclophosphamide; D004164:Diphosphonates; D000077143:Docetaxel; D004317:Doxorubicin; D007093:Imidazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D000077211:Zoledronic Acid; C508053:ERBB2 protein, human
keywords: bisphosphonates; menopausal status; neoadjuvant chemotherapy; zoledronic acid