Abstract C131: Abaloparatide and Paclitaxel Combination Therapy Improves Bone Volume and Tumor Burden in Bone-Metastatic Breast Cancer

Abstract Bone is the most frequent site of both metastasis and recurrence for patients with breast cancer. Tumors dysregulate osteoblasts and osteoclasts in response to bone-derived growth factors, causing further release of growth factors, propagating a feed-forward loop which frequently requires therapeutic intervention. Abaloparatide (ABL) is a bone anabolic which is FDA-approved for osteoporosis and is used off-label for patients with tumor-induced bone loss. Some concerns persist that bone anabolics promote tumor in bone by accelerating turnover, but recently published work suggests that this is not the case. Because chemotherapies such as paclitaxel (PTX) remain the standard of care for cancer patients with distant metastases, it is essential to characterize the impact of ABL in the presence of such agents. Therefore, in this study we describe the first preclinical model of Abaloparatide/Paclitaxel combination therapy in tumor-bearing mice. Athymic nude mice were injected intratibially with MDA-MB-231 triple-negative breast cancer. Mice were administered 80 ug/kg ABL daily subcutaneously, and 15 mg/kg Paclitaxel (PTX) weekly via tail vein. After three weeks, mice were sacrificed and hind limbs collected for microcomputed tomography (uCT) and histomorphometry. Our model achieved the strongest reduction in tumor burden through administration of PTX and ABL as a combination therapy over either as a monotherapy. On average, tumors in PTX+ABL mice occupied 18.4% of marrow volume (as measured by hematoxylin and eosin staining) compared to VEH (91%, p=0.028) or ABL only (77%, p=0.017). The addition of PTX in mice treated with ABL reduced lesion area as measured by x-ray, from 28.7 mm2 to 8.64 mm2, respectively (p=0.039). Notably, no such significance was observed through PTX or ABL alone. Bone volume fraction (BV/TV) was significantly increased in mice receiving PTX+ABL (BV/TV= 0.151) over mice which received either PTX (0.057, p= 0.049) or ABL (0.042, p=0.044) alone. This was accompanied by a decrease (p= 0.013) in trabecular separation in PTX+ABL mice (0.355 mm) in comparison to ABL (0.628 mm) alone.Taken together, our results suggest that bone health and tumor response can be best optimized through a combination of PTX and ABL, but in addition to these data, histomorphometry is currently being performed for bone formation (N.Ob/BS, Ob.S/BS) and resorption (N.Oc/BS, Oc.S/BS) in addition to serum ELISAs for soluble markers (CTX-1, P1NP, TGF-b, and Ca++). Citation Format: Jade Miller, Julie A. Rhoades, Jeremy F. Kane, Marvel Shawkey, Adaline Watkins, Rachelle W. Johnson. Abaloparatide and Paclitaxel Combination Therapy Improves Bone Volume and Tumor Burden in Bone-Metastatic Breast Cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr C131.