Two new studies presented at the San Antonio Breast Cancer Symposium report that women who use bisphosphonates such as Fosamax, Boniva and Actonel for treating osteoporosis have significantly fewer cases of breast cancer. Participants in the National Institutes of Health-sponsored Women's Health Initiative taking bisphosphonates were found to have almost one third fewer cases of breast cancer (3.3%) compared with the nonusers (4.4%) during an average follow-up period of 7.8 years. The study took into account into account breast cancer- and bone density-related factors such as age, weight, smoking, hormone replacement therapy, and vitamin D use. A second Israeli study of postmenopausal women (both with and without breast cancer) found that those with breast cancer were 29 percent less likely to have been taking bisphosphonates. This study also controlled for breast cancer risk factors such as family history and use of other medications. Neither of the studies was a case-control clinical trial and neither is considered definitive. Bisphosphonates have potential side effects, most seriously jaw bone death. The findings are provocative, but it is still too early to use bisphosphonates to prevent breast cancer, according to one of the lead investigators.

Studies confirm and extend previous findings

Numerous other studies have found that bisphosphonates have chemopreventive properties and can reduce the occurrence and number of bone metastases in women diagnosed with invasive breast cancer. The two new studies extend the chemopreventive findings to women who have not been diagnosed with breast cancer. While bisphosphonates are used in some other countries to prevent recurrence of breast cancer, they are not routinely used for this purpose in the U.S. Nor is it likely that bisphosphonates will start to be used to prevent breast cancer among high-risk women based on these two preliminary studies. Below we summarize some of the important findings to date for bisphosphonates and breast cancer:
  • Sequential administration of the chemotherapy agents docetaxel or doxorubicin, followed by the bisphosphonate zoledronic acid, has been found to reduce the growth of bone metastases in animal models of metastatic bone disease in a synergistic manner
  • Long-term bisphosphonate use can result in low serum calcium levels. Combined with the finding that increased bone turnover due to calcium deficiency promotes tumor growth in bone, treatment to correct any calcium insufficiency when using bisphosphonates appears warranted
  • Bisphosphonates may prevent bone loss caused by breast cancer treatments such as aromatase inhibitors. The benefits of bisphosphonate treatment have been shown to be in addition to those derived from supplementation with calcium and vitamin D
  • Risk factors for osteonecrosis of the jaw (which occurs in at approximately 3% of breast cancer patients who take it) include use of dentures and a history of dental extraction. Smoking, periodontitis, and root canal treatment have not been found to increase risk
  • In a study of patients with bone metastases, repeated low-dose therapy with zoledronic acid was shown to induce a long-lasting decrease of vascular endothelial growth factor (VEGF) levels, suggesting a mechanism of action by which bisphosphonates may inhibit cancer spread.

At the moment, bisphosphonates are used to treat women with bone metastases, but not patients with early breast cancer. Several adjuvant trials are in progress to evaluate the role of bisphosphonates in women whose cancers have not metastasized.