Potential role of bone-directed therapy on the superiority of aromatase inhibitors over tamoxifen.

Aromatase inhibitors (AIs) are the current standard of care in postmenopausal women with hormone-responsive breast cancer in adjuvant setting due to their superiority over tamoxifen, in terms of disease-free survival. It is clear that AIs result in bone loss during the course of the treatment and many patients need to receive bisphosphonates and vitamin D supplementation during AI treatment. Emerging evidence shows that bisphosphonates have antitumor effects. In addition, the beneficial effects of vitamin D supplementation on reducing breast cancer incidence and recurrence have recently been published. Thus, could the superiority of AIs over tamoxifen be related to increased need of bisphosphonate use and vitamin D supplementation? Although, at present, there is no concrete evidence of the impact of bone-directed therapy on the improved disease-free survival with AI compared to tamoxifen, we can not disregard this possibility.