Drs Massimo Cristofanilli and Gabriel Hortobagyi review the role of bisphosphonates, which comprise another exciting and controversial treatment for breast cancer. Bisphosphonates are well tolerated, and initial studies have shown an improvement in quality of life for patients with metastatic breast cancer affecting bones. Future research will focus on the mechanisms of action of these agents and the development of molecular markers to monitor response to therapy on these agents. The intriguing question of whether bisphosphonates can cure breast cancer by inhibiting micrometastasis in the adjuvant setting is raised by a small adjuvant trial suggesting that clodronate might improve survival above and beyond standard adjuvant therapy. The more potent third-generation agents are likely candidates to test this hypothesis.
Many questions regarding bisphosphonates remain unanswered.
Zolendronate is currently under investigation to compare its efficacy to pamidronate as an adjunct to usual therapy in the treatment of metastatic breast cancer, and adjuvant trials are being developed to investigate the impact of the addition of bisphosphonates to standard adjuvant therapy. Research in new hormonal treatments for breast cancer is focusing on more potent ways to inhibit the estrogen receptor-mediated cancer progression pathways. New classes of agents are being developed to inhibit both the alpha and beta types of estrogen receptors as well as the ligands that interact with those receptors. The more potent selective inhibitors to the estrogen receptor are likely to have a higher response rate than standard hormonal agents that have partial estrogen-agonistic effects. Many of the new estrogen modulators are being developed for broad spectrum use in the setting of breast cancer prevention.