Recent evidence suggests that certain bone-targeted therapies, including denosumab (Dmab), may enhance antitumor immunity by increasing the infiltration and diversity of T cells within tumors. In breast cancer, women frequently receive immune checkpoint inhibitors (ICIs) together with bone-modifying agents (BMAs), yet the influence of BMAs on immune-related adverse events (irAEs) and treatment efficacy remains largely undefined. We retrospectively analyzed female breast cancer patients treated with pembrolizumab between 2017 and 2024, stratifying them by BMA exposure: zoledronic acid (ZA), Dmab, or none. BMA use was considered relevant if administered within 12 months (ZA) or 6 months (Dmab) prior to ICI, during ICI therapy, or within one month after the last ICI dose.
Among 425 patients, 55 (12.9 percent) received Dmab, 31 (7.3 percent) received ZA, and 339 (80.0 percent) received no BMA. Early-stage breast cancer accounted for 255 patients (60%), while 170 (40 percent) had metastatic disease. After a median follow-up of 19.4 months (95 percent CI, 17.5–20.8), severe irAEs were more common in the Dmab group compared to patients without BMAs (21.8 percent vs 11.5 percent, P = .04). Objective response rates were higher in patients receiving Dmab (48.0%) than in those receiving ZA (31.6%) or no BMA (35.0%), though the difference was not statistically significant (P = .3). These findings suggest that Dmab may increase the risk of severe irAEs and potentially enhance the antitumor efficacy of ICIs in women with breast cancer.
