Bisphosphonates are primarily used for the prevention and treatment of osteoporosis. They inhibit bone resorption and reduce skeletal complications from bone involvement in breast cancer, prostate cancer, and other cancers. Additionally, the more potent aminobisphosphonates inhibit the mevalonate pathway, thereby affecting cell function and survival duration. Also, nitrogen-containing bisphosphonates have been shown to directly induce tumor apoptosis, inhibit angiogenesis, and prevent tumor cell adhesion. It has been suggested that these antiproliferative actions may affect the development of a broad range of cancers, including breast cancer.
A third study, and the first to be published, has found a reduction in the risk for breast cancer among postmenopausal women taking bisphosphonates for the treatment of osteoporosis. The aim of this study was to evaluate whether the use of bisphosphonates is associated with a reduced risk for breast cancer. The new finding, reported in the March 2 issue of the British Journal of Cancer,comes from a case–control analysis of more than 6000 women in Wisconsin, half of whom were diagnosed with invasive breast cancer. It found that the use of bisphosphonates was associated with a 30% reduction in the risk for breast cancer.
This reduction in breast cancer risk is similar to that already reported in 2 other studies, both of which were presented in December 2009 at the San Antonio Breast Cancer Symposium. One was an analysis of more than 150,000 postmenopausal women participating in several Women's Health Initiative studies, which found that bisphosphonate use reduced the risk for invasive breast cancer by 32%. The other involved an analysis of 4575 postmenopausal women in Israel, which found a 34% reduction. Both these studies were not case-controlled.
Accounting for Confounding Factors
The latest study accounts for important confounders, such as body mass index and postmenopausal hormone use. In addition, the reasons for which bisphosphonates were prescribed, such as fractures, height loss, and physician-diagnosed osteoporosis were analysed. There was a suggestion that the use of bisphosphonates was associated with a reduced risk for breast cancer only among women reporting symptoms of bone loss, but this was not statistically significant.
The researchers therefore conclude that "these findings may reflect real benefits due to antitumor mechanisms" of bisphosphonates.
However, the association with a reduction in the risk for breast cancer was seen only among women who were not obese; they were not seen among obese women. This suggests that the inhibitory action of these drugs is related to some threshold effect of hormonal or other growth factors, which are known to be important etiological exposures in breast cancer, the researchers write in their paper.
Dr. Newcomb and colleagues have disclosed no relevant financial relationships. Dr. Guise reports having served on advisory boards for Amgen, Lilly, Novartis, and Roche.
Br J Cancer. 2010 Mar 2;102(5):799-802. Epub 2010 Feb 16.
Bisphosphonates for osteoporosis treatment are associated with reduced breast cancer risk.
Newcomb PA, Trentham-Dietz A, Hampton JM.
Paul P Carbone Comprehensive Cancer Center, University of Wisconsin, 610 Walnut Street, Madison, WI 53726, USA. pnewcomb@fhcrc.org
Abstract
BACKGROUND: Bisphosphanates are used primarily for the prevention and treatment of osteoporosis, and are also indicated for osseous complications of malignancy. In addition to their bone resorption properties, the most commonly used nitrogen-containing bisphosphonate compounds also inhibit protein prenylation, and thus may exert anti-tumour properties. METHODS: To evaluate whether the use of these drugs may be associated with cancer, specifically breast cancer, we conducted a population-based case-control study in Wisconsin from 2003 to 2006. Participants included 2936 incident invasive breast cancer cases and 2975 population controls aged < 70 years. Bisphosphonate use and potential confounders were assessed by interview. RESULTS: Using multivariable logistic regression, the odds ratio for breast cancer in current bisphosphonate users compared with non-users was 0.67 (95% confidence interval 0.51-0.89). Increasing duration of use was associated with a greater reduction in risk (P-trend=0.01). Risk reduction was observed in women who were not obese (P-interaction=0.005). CONCLUSION: These results are suggestive of an additional benefit of the common use of bisphosphonates, in this instance, the reduction in breast cancer risk.
Edited From MedscapeCME Clinical Briefs
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