Intravenous bisphosphonates for breast cancer: impact on patient outcomes and scientific concepts

Among women worldwide, breast cancer is the most common malignancy and a leading cause of death, accounting for approximately 6% of all cancer deaths globally. The predilection of breast cancer to metastasize to bone provides a strong rationale that antiresorptive agents such as bisphosphonates may have the potential to prevent disease recurrence. Bisphosphonates are established therapies for bone loss and for preventing skeletal-related events (SREs) from bone metastases. Moreover, intravenous nitrogen-containing bisphosphonates, such as zoledronic acid, have been shown to block multiple steps in tumor metastasis (e.g., angiogenesis, invasion, and adhesion). Recent clinical data from ABCSG-12, ZO-FAST, and AZURE demonstrate that zoledronic acid can significantly improve disease-free survival (DFS) in the adjuvant breast cancer setting in women who are naturally postmenopausal or have endocrine therapy-induced menopause. Furthermore, the ABCSG-12 trial showed durable disease-free survival benefits 2 years after completion of adjuvant therapy. These data suggest a potential role for zoledronic acid beyond bone health in breast cancer. Although it is too early to determine which patients are most likely to benefit from the anticancer potential of bisphosphonates, future research will help further guide therapy in this setting.