Oral Bisphosphonates May Significantly Reduce Breast Cancer

Results of a new analysis of data from the Women's Health Initiative (WHI) observational study showed that women who used bisphosphonates, which are commonly prescribed bone-strengthening pills, had significantly fewer invasive breast cancers than women who did not use bisphosphonates. These findings were presented at the CRTC-AACR San Antonio Breast Cancer Symposium.

In the 150,000-plus cohort of generally healthy postmenopausal women, the researchers found that women who used bisphosphonates, mostly alendronate, which is sold as Fosamax (alendronate sodium) by Merck, had 32% fewer cases of invasive breast cancer compared to women who did not use such drugs.

"The idea that bisphosphonates could reduce breast cancer incidence is very exciting because there are about 30 million prescriptions for these agents written annually in the United States targeting bone health, and more could easily be used to counteract both osteoporosis and breast cancer," said the study's lead investigator, Rowan Chlebowski, M.D., Ph.D., medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center.

The concept arose from findings in a report on an adjuvant breast cancer trial where use of the bisphosphonate zoledronic acid given intravenously every six months resulted in fewer contralateral breast cancers.

"It appeared to make bone less hospitable to breast cancer," Chlebowski said.

However, since bisphosphonates are prescribed for women with low bone mineral density and low bone mineral density has been associated with lower breast cancer incidence, a means to control for potential differences between women prescribed bisphosphonate and those not prescribed bisphosphonate in the cohort was needed.

Given that, Chlebowski and colleagues devised a way to control for use of bisphosphonates in the WHI. About 10,000 of the participants had bone mineral density analysis as part of the study, and for the rest they used a 10-item hip fracture predictive score to measure bone density. The researchers were able to correlate the findings from the women who had bone mineral density tests to findings from the predictive score in order to correct for any potential difference in bone density in women using bisphosphonates compared to non-users.

Studying 2,216 WHI participants who were using bisphosphonates when they entered the study, the researchers found that only 64 women developed breast cancer, and most of those cases (50) were estrogen receptor positive. Overall, there was a mean 32 percent fewer breast cancers in women using bisphosphonates compared to women who did not. There were 30 percent fewer estrogen receptor-positive cancers and 34 percent fewer entry receptor-negative cancers in bisphosphonate users. The latter finding was not statistically significant as there were very few receptor-negative cases.

"Bisphosphonates reduce angiogenesis and stimulate immune cells responsible for tumor cell surveillance as potential mediators," Chlebowski said. "This association needs to be studied further. While we currently have several options for reducing receptor-positive breast cancers, none are available for receptor-negative cancers."

Several ongoing adjuvant breast cancer trials evaluating oral and intravenous bisphosphonate will be available in the near future to provide randomized clinical trial evidence regarding their influence on new contralateral breast cancer risk, Chlebowski said.

For more information:

•  Onco'Zine - The International Cancer Network