title: Effects of neoadjuvant chemotherapy with or without zoledronic acid on pathological response: A meta-analysis of randomised trials.
abstract: OBJECTIVE
  The addition of bisphosphonates to adjuvant therapy improves survival in postmenopausal breast cancer (BC) patients. We report a meta-analysis of four randomised trials of neoadjuvant chemotherapy (CT) +/- zoledronic acid (ZA) in stage II/III BC to investigate the potential for enhancing the pathological response.
  
  
  METHODS
  Individual patient data from four prospective randomised clinical trials reporting the effect of the addition of ZA on the pathological response after neoadjuvant CT were pooled. Primary outcomes were pathological complete response in the breast (pCRb) and in the breast and lymph nodes (pCR). Trial-level and individual patient data meta-analyses were done. Predefined subgroup-analyses were performed for postmenopausal women and patients with triple-negative BC.
  
  
  RESULTS
  pCRb and pCR data were available in 735 and 552 patients respectively. In the total study population ZA addition to neoadjuvant CT did not increase pCRb or pCR rates. However, in postmenopausal patients, the addition of ZA resulted in a significant, near doubling of the pCRb rate (10.8% for CT only versus 17.7% with CT+ZA; odds ratio [OR] 2.14, 95% confidence interval [CI] 1.01-4.55) and a non-significant benefit of the pCR rate (7.8% for CT only versus 14.6% with CT+ZA; OR 2.62, 95% CI 0.90-7.62). In patients with triple-negative BC a trend was observed favouring CT+ZA.
  
  
  CONCLUSIONS
  This meta-analysis shows no impact from the addition of ZA to neoadjuvant CT on pCR. However, as has been seen in the adjuvant setting, the addition of ZA to neoadjuvant CT may augment the effects of CT in postmenopausal patients with BC.
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J R
authors.initials: JR
authors.lastname: Kroep
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Charehbili
authors.affiliation: Sheffield Cancer Research Centre, Weston Park Hospital, Sheffield, United Kingdom.
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.affiliation: Washington University School of Medicine, St. Louis, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Aft
authors.affiliation: Hirosaki Municipal Hospital, Aomori, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.affiliation: Sheffield Cancer Research Centre, Weston Park Hospital, Sheffield, United Kingdom.
authors.forename: M C
authors.initials: MC
authors.lastname: Winter
authors.affiliation: Washington University School of Medicine, St. Louis, USA.
authors.forename: K
authors.initials: K
authors.lastname: Weilbaecher
authors.affiliation: Niigata University, Niigata, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Akazawa
authors.affiliation: Clinical Trials Research Unit, Leeds, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Hinsley
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Putter
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Liefers
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: J W R
authors.initials: JWR
authors.lastname: Nortier
authors.affiliation: Kobe Kaisei Hospital, Kobe, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kohno
mesh_terms: D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D004164:Diphosphonates / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008207:Lymphatic Metastasis; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D017698:Postmenopause; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Bisphosphonates; Breast cancer; Chemotherapy; Neoadjuvant; Pathological complete response; Zoledronic acid