Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2010 Mar 30;102(7):1099-105.
doi: 10.1038/sj.bjc.6605604. Epub 2010 Mar 16.

The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer

R E Coleman  1 , M C Winter, D Cameron, R Bell, D Dodwell, M M Keane, M Gil, D Ritchie, J L Passos-Coelho, D Wheatley, R Burkinshaw, S J Marshall, H Thorpe; AZURE (BIG01/04) Investigators
Affiliations
Randomized Controlled Trial

The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer

R E Coleman et al. Br J Cancer. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusion: These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies.

PubMed Disclaimer

Conflict of interest statement

RE Coleman has received honoraria and consulting fees from Novartis, Amgen, Roche, and Pfizer and has previously given expert testimony on behalf of Novartis. D Cameron received honoraria from Novartis and Roche. D Dodwell received adhoc consultancy/ad boards and lecture payments from Roche, Astra Zeneca and Novartis. R Burkinshaw is in receipt of research funding from Novartis Pharmaceuticals. All other authors have no conflict of interest.

Figures

Figure 1
Figure 1
AZURE trial schema. (Does adjuvant zoledronic acid reduce recurrence in patients with high-risk localised breast cancer?)
See this image and copyright information in PMC

References

    1. Bear HD, Anderson S, Smith RE, Geyer Jr CE, Mamounas EP, Fisher B, Brown AM, Robidoux A, Margolese R, Kahlenberg MS, Paik S, Soran A, Wickerham DL, Wolmark N (2006) Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24: 2019–2027 - PubMed
    1. Buzdar AU (2007) Preoperative chemotherapy treatment of breast cancer – a review. Cancer 110: 2394–2407 - PubMed
    1. Carey LA, Metzger R, Dees EC, Collichio F, Sartor CI, Ollila DW, Klauber-DeMore N, Halle J, Sawyer L, Moore DT, Graham ML (2005) American Joint Committee on Cancer tumor-node-metastasis stage after neoadjuvant chemotherapy and breast cancer outcome. J Natl Cancer Inst 97: 1137–1142 - PubMed
    1. Chen AM, Meric-Bernstam F, Hunt KK, Thames HD, Oswald MJ, Outlaw ED, Strom EA, McNeese MD, Kuerer HM, Ross MI, Singletary SE, Ames FC, Feig BW, Sahin AA, Perkins GH, Schechter NR, Hortobagyi GN, Buchholz TA (2004) Breast conservation after neoadjuvant chemotherapy: the MD Anderson Cancer Center experience. J Clin Oncol 22: 2303–2312 - PubMed
    1. Coleman R (2007) Potential use of bisphosphonates in the prevention of metastases in early-stage breast cancer. Clin Breast Cancer 7(Suppl 1): S29–S35 - PubMed

Publication types