The evolving role of zoledronic acid in early breast cancer

Most women with early breast cancer (BC) have an excellent prognosis and will remain disease-free for many years after treatment. However, bone-specific side effects of cancer therapies can have a negative effect on patients' long-term bone health. The accelerated bone loss associated with BC therapies, especially endocrine therapy, can put women at risk for osteoporosis and fractures later in life. Recent treatment guidelines have now begun to address the need for bone-preserving measures to be included in adjuvant therapy regimens. Bisphosphonates have long been used to treat osteoporosis, as well as bone metastases in patients with advanced cancers. Furthermore, in the adjuvant BC setting, the intravenous bisphosphonate zoledronic acid has emerged to play an important role. Several large, randomized phase III trials involving a total of approximately 4,000 premenopausal and postmenopausal women with early BC demonstrated the bone-protective effects of adjuvant zoledronic acid (4 mg every 6 months). Additionally, these same trials also showed significant improvement in disease-free survival for patients receiving adjuvant endocrine therapy plus zoledronic acid that was over and above the benefit achieved with endocrine therapy alone. The results of these zoledronic acid trials will be reviewed herein, and evidence supporting the antitumor effects of adjuvant zoledronic acid will be discussed.