Expanding role of bisphosphonates in the management of early breast cancer

Current expert guidelines support tamoxifen alone or tamoxifen plus ovarian suppression as adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer. Aromatase inhibitors have succeeded tamoxifen as the endocrine manipulation of choice in the treatment of postmenopausal patients. However, their use as monotherapy has traditionally been contraindicated in premenopausal women because the suppression of peripheral aromatase results in reduced feedback to the hypothalamus, and an increase in ovarian stimulation. The Austrian Breast and Colorectal Cancer Study Group trial 12 randomized premenopausal women with endocrine-responsive early breast cancer receiving the luteinizing hormone-releasing hormone agonist goserelin to tamoxifen or anastrozole without finding a significant efficacy advantage for either arm. A further randomization within the study assigned patients to receive zoledronic acid or not. Intriguingly, the addition of the bisphosphonate to adjuvant endocrine therapy significantly improved disease-free survival in the trial population. These data support the hypothesis that bisphosphonates can reduce rates of distant metastases by manipulation of the bone microenvironment, or potentially, by a direct anti-tumor effect. We discuss the potential impact of this study on clinical practice and the important issue of bone health in young women with breast cancer.