Expanding role of bisphosphonates in the management of early breast cancer

Abstract

Evaluation of: Gnant M, Mlineritsch B, Schippinger W et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N. Engl. J. Med. 360(7), 679–691 (2009)

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.

Keywords::

• aromatase inhibitors
• breast cancer
• ovarian suppression
• tamoxifen
• zoledronic acid

Financial & competing interests disclosure

Ben H Park is a consultant for GlaxoSmithKline and has received research funding in the past. This is managed according to University policy on conflicts of interest. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.