Abstract B13: Plasma G-CSF levels are predictive of lack of response to zoledronic acid treatment in reducing breast cancer recurrence

Some breast cancer patients have no evidence of metastatic disease at the time of original diagnosis, yet ~30-40% of patients will experience recurrent breast cancer. Over 90% of breast cancer deaths occur due to distant spread of the disease, and bone is the most common site of breast cancer metastasis. Bisphosphonates, such as zoledronic acid (ZA), are used to treat patients with osteolytic disease, including metastatic breast cancer. ZA has been demonstrated to reduce disseminated tumor cells (DTCs) and breast cancer recurrence, but not all patients see this benefit and it is not yet clear what predicts benefit from adjuvant ZA treatment; the mechanism of action for this effect of ZA in reducing breast cancer remains undetermined. Here, we establish that ZA renders osteoclast progenitor cells (OCPs) tumor suppressive, primarily by directing their lineage potential. In instances where the OCP lineage potential was modulated via systemic or tumor-derived granulocyte-colony stimulating factor (G-CSF), OCPs did not differentiate into tumor-suppressive populations but instead into mature osteoclasts. High G-CSF was sufficient to abrogate the tumor-suppressive effect of ZA. Furthermore, we determined that in a subset of patient plasma samples from the AZURE clinical trial where stage II/III breast cancer patients were randomized to receive standard systemic treatment alone with adjuvant ZA treatment, patients who had baseline plasma G-CSF levels >23 pg/mL had reduced disease-free survival as assessed over a 10-year period post treatment initiation compared to patients with baseline plasma G-CSF levels Citation Format: Jessalyn M. Ubellacker, Ninib Baryawno, Nicolas Severe, Molly J. DeCristo, Jaclyn Sceneay, Marie-Therese Haider, Catherine S. Rhee, Yuanbo Qin, Ingunn Holen, Walter M. Gregory, Janet E. Brown, Robert E. Coleman, David T. Scadden, Sandra S. McAllister. Plasma G-CSF levels are predictive of lack of response to zoledronic acid treatment in reducing breast cancer recurrence [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B13.