The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer
Open Access
- 16 March 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 102 (7), 1099-1105
- https://doi.org/10.1038/sj.bjc.6605604
Abstract
Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups. In total, 205 patients received neoadjuvant CT±ZOL (CT+ZOL, n=102; CT, n=103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n=195), outcome differences between groups were assessed adjusting for potential response modifiers. Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CT+ZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5–20.4 mm; P=0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CT+ZOL group (P=0.146). There was no difference in axillary nodal involvement (P=0.6315). These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies.Keywords
This publication has 27 references indexed in Scilit:
- Sustained inhibition of tumor growth and prolonged survival following sequential administration of doxorubicin and zoledronic acid in a breast cancer modelInternational Journal of Cancer, 2009
- Endocrine Therapy plus Zoledronic Acid in Premenopausal Breast CancerNew England Journal of Medicine, 2009
- Staging of Breast Cancer in the Neoadjuvant SettingCancer Research, 2008
- Preoperative Therapy in Invasive Breast Cancer: Pathologic Assessment and Systemic Therapy Issues in Operable DiseaseJournal of Clinical Oncology, 2008
- Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006Annals Of Oncology, 2007
- Preoperative chemotherapy treatment of breast cancer—A reviewCancer, 2007
- Neoadjuvant chemotherapy for operable breast cancerBritish Journal of Surgery, 2007
- Sequential Preoperative or Postoperative Docetaxel Added to Preoperative Doxorubicin Plus Cyclophosphamide for Operable Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27Journal of Clinical Oncology, 2006
- Breast Conservation After Neoadjuvant Chemotherapy: The M.D. Anderson Cancer Center ExperienceJournal of Clinical Oncology, 2004
- Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST piBritish Journal of Cancer, 1996