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Open Access Research article

Prognostic and predictive value of clinical and biochemical factors in breast cancer patients with bone metastases receiving "metronomic" zoledronic acid

Xinmin Zhao1, Xiaofeng Xu2, Qunling Zhang1, Zhen Jia1, Si Sun1, Jian Zhang1, Biyun Wang1, Zhonghua Wang1 and Xichun Hu1*

Author Affiliations

1 Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong An Road, Shanghai 200032, China

2 Department of Clinical Laboratory, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, No. 270, Dong An Road, Shanghai 200032, China

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BMC Cancer 2011, 11:403  doi:10.1186/1471-2407-11-403

Published: 22 September 2011

Abstract

Background

To assess prognostic and predictive effects of clinical and biochemical factors in our published randomized study of a weekly low dose (metronomic arm) versus a conventional dosage of zoledronic acid (conventional arm) in breast cancer patients with bone metastases.

Methods

Treatment outcome of 60 patients with bone metastases were used to assess impacts of following potential prognostic factors, estrogen receptor status, lymph node status, 2 year-disease free interval (DFI), numbers of chemotherapy regimens administered, interventions, and serum levels of VEGF, N-telopeptide of type I collagen (NTx), CEA, and CA 15-3.

Results

In univariate analyses, patients pretreated with 2 or fewer chemotherapy regimens, ER-positive tumors, 3 or fewer lymph nodes, DFI of more than 2 years, serum VEGF of less than 500 pg/mL after 3 months of intervention, serum CEA and CA 15-3 of less than ULN, and baseline serum NTx of less than 18 nM BCE had significantly longer progression free survival (PFS). The multivariate analysis showed that ER positivity (hazard ratio [HR], 0.295; 95% confidence interval [CI], 0.141-0.618; P = 0.001), serum VEGF of less than 500 pg/mL after 3 months of intervention (HR, 2.220; 95% CI, 1.136-4.338; P = 0.020), baseline serum NTx of less than 18 nM BCE (HR, 2.842; 95% CI, 1.458-5.539; P = 0.001), and 2 or fewer chemotherapy regimens received (HR, 7.803; 95% CI, 2.884-21.112; P = 0.000) were associated with a better PFS. When evaluating the predictive effect of the biochemical factors, an interaction between NTx and zoledronic acid intervention was shown (P = 0.005). The HR of weekly low dose versus a conventional dosage of zoledronic acid was estimated to be 2.309 (99% CI, 1.067-5.012) in patients with baseline serum NTx of more than 18 nM BCE, indicating a superiority of weekly low dose of zoledronic acid.

Conclusions

ER, serum VEGF level after intervention, and numbers of chemotherapy regimens administered are prognostic but not predictive factors in breast cancer patients with bone metastases. Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid.

Trial registration

ClinicalTrials.gov unique identifier: ClinicalTrials.gov: NCT00524849

Keywords:
Advanced breast cancer; bone metastases; zoledronic acid; VEGF; N-telopeptide; prognosis; predictive factors