Abstract PS3-08-19: Evaluation of stable calcium isotope ratios in women undergoing neoadjuvant chemotherapy (NACT) with and without denosumab (GeparX)

Abstract Background: Blood and bone Ca isotope compositions are in isotopic equilibrium. During equilibrium between bone material absorption and resorption the blood Ca isotope composition remains stable. However, when bone resorption is persistently greater than bone absorption, as seen in osteoporosis, the blood Ca isotope ratio decreases. This indicates a net shift of calcium from the bone into the blood. The calcium isotope marker (CIM) is a novel biomarker that sensitively detects changes in bone calcium balance in humans. For the first time, this study aims to evaluate the effects of neoadjuvant chemotherapy (NACT), with and without denosumab (Dmab), on bone calcium balance in postmenopausal women with early breast cancer enrolled in the GeparX trial (NCT02682693). Methods: This analysis was conducted on a predefined cohort of the patients (pts) enrolled in the GeparX trial (Blohmer, JAMA Oncol. 2022), specifically including postmenopausal pts with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer who received NACT with weekly nab-paclitaxel followed by epirubicin/cyclophosphamide. Patients included in this cohort were randomized to receive Dmab or not in addition to NACT. Eligible pts had two serum samples available: one prior to treatment and one after completion of NACT. In total, 20 pts included in this study were treated in the NACT + Dmab arm and 29 received NACT alone. Paired serum samples (collected before therapy and before surgery) were analyzed for CIM ratios. Results: A total of 98 serum samples were tested for CIM serum levels and valid measurements were obtained for all. Pre-treatment mean CIM values were comparable in both cohorts (mean±SD -0.87±0.16 ‰ vs. -0.94±0.19 ‰; p=0.115; without vs. with Dmab, respectively), indicating a net loss of calcium; however, the difference was not statistically significant. In pts treated with NACT alone, a significant decrease in CIM-serum levels to -1.02±0.17 ‰ was detected signifying bone calcium loss (p