Abstract P6-07-18: A pilot study of the impact of a single dose of zolendronic acid on biomarkers in breast cancer

Backgrounds: In randomized trials for early stage breast cancer, patients who received adjuvant zolendronic acid (ZA) had superior disease-free survival and greater tumor shrinkage. Preclinical data suggest that ZA has anti-cancer properties by modulating angiogenesis and tumor immune environment. This is the pilot study to assess changes in tumor biomarkers and immunological function in response to a single dose of ZA in paired tumor specimens (from core biopsy and definitive surgery). Methods: Postmenopausal women with early stage invasive ductal breast carcinoma who have estrogen receptor and/or progesterone receptor positive tumor for which a lumpectomy or mastectomy was planned prior to systemic therapy were enrolled. A single dose of ZA 4mg IV was given 10-14 days prior to their planned definitive surgery. 14 biomarkers in tumor tissue was assayed; 10 by gene microarray (VEGF, IL1β, IL-6, MMP-1, MMP-2, MMP-9, TGF, Interferon α and STAT3)) and 4 by RT-PCR(P13K, PTEN, IGF-1-R, EGFR. Patient blood samples were drawn at baseline, at 48-72hrs after the single dose of ZA and at the time of surgery and assayed for cytokines and chemokines by using 30-plex Luminex panels. Results: Eight patients were enrolled in the study (median age 65 and range (57-75); 4 caucatians, 2 hispanic and 1 asian; 6 stage I, 1 stage II and 1 stage III). 30-plex luminex assays showed MIG, IP-10 and IL-12 were found to increase in Day 1-3 of ZA therapy from baseline and normalized by Day 10-24. MCP-1, IL2R, MIP-1b and Eotaxin were found to have changes in Day 1-3 from baseline and mix outcome by Day 10-24. EGF, G-CSF, HGF, IFN-alpha and IFN-gamma and RANTES showed no clear pattern among eight patients. Tumor markers and proteomics from pair tumor samples will be presented. Conclusions: Changes in multiple tumor biomarkers and immunological markers, MIG, IP-10, IL-12, MCP-1, IL2R, MIP-1b, Eotaxin, IFN-alpha and IFN-gamma are seen within 2 weeks of a single dose of ZA. Citation Format: Cho M, Gong J, Chen S, Yu H, Wong L, Kruper L, Mortimer J. A pilot study of the impact of a single dose of zolendronic acid on biomarkers in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-18.