Abstract P6-05-17: A study of investigating biologic markers of anti-tumor effects of zoledronic acid and taxane-based chemotherapy for metastatic breast cancer in bone: A prospective, multi-center, non-randomized study (BEAT-ZO) (KCSG BR10-13)
Authors: Choi YJ , Bae JW , Kim HJ , Kang SY , Park YH , Lee S , Jung KH , Oh H-S , Choi IS , Lee K-H , Lee S-E , Park KH 
Published: August 2014

Abstract
Introduction
Currently the predictive factors for taxane(T)-zoledronic acid(ZA) combination therapy in breast cancer patient with bone metastasis have not been established except tumor biology. The aim of this study is to investigate potential biologic markers of anti-tumor effects of and T-ZA for metastatic breast cancer(MBC) in bone.
Methods
Patients(pts) with MBC in bone being treated with docetaxel or paclitaxel based chemotherapy and ZA for the first time in metastatic setting were enrolled. Blood samples were collected serially at baseline, after 2 cycles to examine markers for angiogenesis(VEGF, VEGFR2, FGF-2, PDGF-AA), immune modulation (IL-2, IFN-γ, MCP-2, IL-10, TGF-β, IL-12, TNF-α, IL-17, IL-6) and apoptosis (TRAIL).
Results
Of enrolled total 58 pts, 31 pts (median age 49; ECOG 0-1 96.8%; menopause 58.1%; invasive ductal carcinoma 92.9%; ER-(+) 77.4%; HER2-(+) 35.5%; visceral metastasis 35.5%) were included in this preliminary analysis.
Fifteen pts received docetaxel-based chemotherapy and the remainder were treated with paclitaxel-based chemotherapy. Median 6 (range: 1 – 23) cycles per pt were administered. In per-protocol analysis, overall RR was 55.6% [95% CI: 37.3 – 72.4]. After the median follow-up of 13.67 months(mo.), median PFS was 9.13 mths [95% CI: 3.25 – 15.02]. Osteonecrosis of the jaw was reported in only one patient (3.2%).
In the baseline biomarker analysis, the pts with triple-negative breast cancer (TNBC) showed significantly higher VEGF level than hormone (+) or HER-2 (+) pts (518.7 vs 151.6 and 179.2 pg/ml, p = 0.041). Median baseline TRAIL was significantly higher in the postmenopausal women than the premenopausal women (52.0 vs 32.0 pg/ml, p = 0.038).
For the group as a whole, there was a borderline significant reduction in median serum MCP-2 level (41.4 to 34.1 pg/ml, p = 0.066) and an increasing tendency in median serum TRAIL level (44.7 to 54.5 pg/ml, p = 0.080) after 2 cycles of treatment. Median percentage reduction in serum VEGF in the TNBC group was -50.0% compared with +37.7% in others (p = 0.099). Median changes in MCP-2 was -36.4% in hormone (+) group compared with +7.6% in others (p = 0.008).
The pts who were progression free at 6 mths showed significant increase in median TNF-α after 2cycles of treatment, while the pts who experienced disease progression within 6 mths showed significant decrease in TNF-α level (p = 0.028) and there was a similar tendency in TRAIL level (p = 0.157).
The pts with increase of serum TNF-α or TRAIL levels from baseline showed significant improvement of PFS comparing the pts with no change or decrease of TNF-α and TRAIL levels (13.3 vs 5.93 mths, p = 0.012).
We are planning to perform additional analysis. The significance of serum TGF-β level on prognosis and the data of the remainder will be presented on the poster.
Conclusion
In this study, baseline levels and changes of biomarkers suggest potentially relevant interactions between menopausal status, tumor biology and treatment. Especially, TNF-α and TRAIL may be potential early marker for zoledronic acid and taxane-based chemotherapy for MBC in bone. Larger studies are needed to validate these complex interactions.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-05-17.