Bisphosphonate use associated with decreased risk for breast cancer

New data suggest an additional benefit of bisphosphonates on breast cancer, especially with increased duration of use.

Researchers conducted a population-based, case-control study to assess the association between bisphosphonate use and risk for breast cancer. The study included 2,936 incident invasive breast cancer cases and 2,975 matched controls. All women were aged 20 to 69 years during 2003 and 2006.

The women were interviewed about their bone health, including history of fractures, diagnosis of osteoporosis and history of bisphosphonate use. Current bisphosphonate use was defined as “use in the year before the reference year and former users who had taken bisphosphonates at any time before this period.”

The OR for breast cancer among current bisphosphonate users vs. nonusers was 0.67 (95% CI, 0.51-0.89).

Extended duration of bisphosphonate use was associated with the greatest decrease in breast cancer risk (P=.01). Women who used bisphosphonates for more than two years had a nearly 40% reduction in risk compared with women who did not.

The protective effect of bisphosphonates was observed only in women who were not obese (P=.005).

“Obese women may have elevated estrogen levels, so underlying hormones may influence the ability of bisphosphonates to reduce breast cancer risk,” the researchers said in a press release.

Further analysis of the inverse effects of bisphosphonate use indicated that it was only associated with a reduced risk for breast cancer in women who reported symptoms of bone loss caused by postmenopausal fractures, osteoporosis and decreases in height.

The researchers reported no adverse effects associated with bisphosphonate use on age, smoking status or hormone therapy. - by Jennifer Southall

Newcomb PA. British J Cancer. 2010;102:799-802.

Bisphosphonates inhibit the enzyme farnesyl pyrophosphate, important in cholesterol metabolism. This inhibition prevents the production of small molecules that are cast off in the process of making cholesterol. These small molecules are important in the activity of the osteoclast and, therefore, their decreased production caused by the bisphosphonate, impairs osteoclast action. This same decreased production of these small molecules may also impair tumor growth. However, there is another way of looking at the data. Some women who have low bone mass, fracture and wind up on bisphosphonates, may for a number of reasons, have low estrogen. The low estrogen may protect them against breast cancer but cause them to develop fragile bones and be given bisphosphonates. In other words, the bisphosphonate may have nothing to do with the reduction in breast cancer. Randomized trials are needed to sort this out.

- Donald A. Bergman, MD
Clinical Professor of Medicine, Mount Sinai School of Medicine