Radiation Therapy and Bone-Modifying Agents for Bone Metastases in Patients with Breast Cancer: Clinical and in Vitro Study

Abstract

Bone-modifying agents (BMAs) are reportedly associated with a decrease in skeletal-related events (SREs), which include pathologic fractures, spinal cord compression, bone surgery, radiation therapy (RT) for bones, and hypercalcemia. Therefore, BMAs are frequently used for treating patients with bone metastases. Although RT is often used to prevent SREs, RT is itself a type of SRE. Here we evaluated the usefulness of RT combined with BMA compared with BMA alone for bone metastasis treatment. In this clinical study, osteolytic bone metastases of the spine or pelvic bone in patients with breast cancer were evaluated. Tomographic imaging was used to evaluate 28 lesions before and after RT + BMA and 15 lesions before and after BMAs alone. The median age of the participants was 62 (range, 33-82) years. None of the lesions were treated with chemotherapy or molecular targeted drugs during the follow-up period for evaluating local responses. For calculating the overall survival (OS) rates, the periods in which chemotherapy or molecular targeted drugs were used after RT and/or BMAs were included. The median follow-up period was 18 (range, 2-90) months. Response to therapy was evaluated based on the revised Response Evaluation Criteria in Solid Tumors guidelines version 1.1. Patients with complete or partial response were considered as responders, whereas those with stable or progressive disease were considered as non-responders. For the in vitro study, a breast cancer cell-line, MCF-7, was analyzed using a colony formation assay. Cells were incubated with various concentrations of zoledronic acid (ZA; 0-100 μM), followed by irradiation with 0 (control), 2, 4, and 8 Gy. After 14 days, the colonies were stained with crystal violet and counted. Most osteolytic lesions treated with RT + BMA showed bone reformation (75.0%). Decreased fluorodeoxyglucose uptake and improved signal abnormalities were also confirmed using magnetic resonance imaging. Although some osteolytic lesions improved after using BMAs alone (33.3%), most remained unchanged or gradually worsened. The rate of improvement with RT + BMA was significantly higher than that with BMAs alone (p = 0.001). The cumulative incidence rate of response at 6 months was 54.4% in the RT + BMA group and 27.5% in the BMAs alone group. The OS rate in the responder group (83.1% at 1 year) was significantly higher than that in the non-responder group (37.5% at 1 year; p = 0.029). Colony formation decreased in a ZA concentration- and dose-dependent manner.Abstract 3340; Table 1TreatmentCR or PRSD or PDBMA alone510RT + BMA217 Open table in a new tab RT + BMA is more useful than BMAs alone in both clinical and in vitro situations.