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• W2153711239 abstract "Abstract Purpose: Clinical trials in early breast cancer have suggested that benefits of adjuvant bone-targeted treatments are restricted to women with established menopause. We developed models that mimic pre- and postmenopausal status to investigate effects of altered bone turnover on growth of disseminated breast tumor cells. Here, we report a differential antitumor effect of zoledronic acid (ZOL) in these two settings. Experimental design: Twleve-week-old female Balb/c-nude mice with disseminated MDA-MB-231 breast tumor cells in bone underwent sham operation or ovariectomy (OVX), mimicking the pre- and postmenopausal bone microenvironment, respectively. To determine the effects of bone-targeted therapy, sham/OVX animals received saline or 100 μg/kg ZOL weekly. Tumor growth was assessed by in vivo imaging and effects on bone by real-time PCR, micro-CT, histomorphometry, and measurements of bone markers. Disseminated tumor cells were detected by two-photon microscopy. Results: OVX increased bone resorption and induced growth of disseminated tumor cells in bone. Tumors were detected in 83% of animals following OVX (postmenopausal model) compared with 17% following sham operation (premenopausal model). OVX had no effect on tumors outside of bone. OVX-induced tumor growth was completely prevented by ZOL, despite the presence of disseminated tumor cells. ZOL did not affect tumor growth in bone in the sham-operated animals. ZOL increased bone volume in both groups. Conclusions: This is the first demonstration that tumor growth is driven by osteoclast-mediated mechanisms in models that mimic post- but not premenopausal bone, providing a biologic rationale for the differential antitumor effects of ZOL reported in these settings. Clin Cancer Res; 20(11); 2922–32. ©2014 AACR." @default.
• W2153711239 created "2016-06-24" @default.
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• W2153711239 date "2014-05-29" @default.
• W2153711239 modified "2023-10-16" @default.
• W2153711239 title "Zoledronic Acid Has Differential Antitumor Activity in the Pre- and Postmenopausal Bone Microenvironment <i>In Vivo</i>" @default.
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• W2153711239 doi "https://doi.org/10.1158/1078-0432.ccr-13-1246" @default.
• W2153711239 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4040234" @default.
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• W2153711239 hasPublicationYear "2014" @default.
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