Although all IV and oral bisphosphonates have been shown to reduce the incidence of skeletal complications compared with placebo, observation of a single endpoint used in the randomized, placebo-controlled trials discussed above in similar populations of breast cancer patients with bone metastases demonstrates that zoledronic acid significantly reduced the percentage of patients with at least one SRE by 40% relative to placebo at one year (p=0.001).¹⁰ IV pamidronate (90mg) significantly reduced, but to a lesser extent, the number of patients experiencing at least one SRE by approximately 22% relative to placebo at two years (p<0.001),3 and both IV ibandronate (6mg) and oral ibandronate (50mg/day) failed to significantly reduce the percentage of patients with a new bone event relative to placebo at one year (18% and 13% relative reductions, respectively).^11,14

Conclusion

Patients with advanced breast cancer are at high risk for developing bone metastases, which often result in painful skeletal complications that can negatively affect quality of life. Both oral and IV bisphosphonates provide clinical benefits for these patients; however, IV bisphosphonates have demonstrated more consistent and durable benefits without the GI toxicity, variable absorption, and lack of compliance associated with oral bisphosphonates. Current ASCO guidelines recommend the use of either IV pamidronate or zoledronic acid for patients with advanced breast cancer and bone metastases.7 However, zoledronic acid has demonstrated superior efficacy compared with pamidronate in patients with breast cancer, and zoledronic acid can be administered via a more convenient 15-minute infusion. Zoledronic acid has therefore rapidly become the new international standard of care for the treatment of bone metastases in patients with breast cancer. Currently, studies are ongoing to investigate the role of oral and IV bisphosphonates for the prevention of cancer treatment-induced bone loss^31,32 and the prevention of bone metastases.33 Recently, analysis of a large, five-year, multicenter trial demonstrated that oral clodronate significantly reduced the incidence of bone metastases in patients with primary operable stage I to III breast cancer compared with placebo.20 Therefore, the role of bisphosphonates in the treatment of breast cancer is likely to expand. In the future, bisphosphonates will not only be administered for the prevention of skeletal morbidity in patients with advanced metastatic disease, but may also be prescribed as early adjuvant therapy for the maintenance of bone health in these patients throughout their continuum of care.