Abstract
Abstract Bisphosphonates are traditionally used for treatment of osteoporosis and more recently for treatment and prevention of bone metastases in various malignancies. The use of 2nd-generation oral bisphosphonates has been reported to reduce the risk of developing breast and colon cancer but their influence on cancer survival has not been studied. Methods Two large cohorts of consecutively diagnosed cases with breast or colorectal cancer were studied for the association between use of 2nd-generation oral bisphosphonates and cancer survival. Using computerized prescription records, sustained use of alendronate/risedronate was assessed in postmenopausal women with newly diagnosed breast (n = 2,843) or colorectal cancer (n = 1,706). Overall survival and cancer-specific survival were evaluated using time dependent analysis. Results Postmenopausal women with breast cancer previously unexposed to bisphosphonates who used 2nd-generation bisphosphonates after diagnosis for at least one year had a significantly better survival than non-users, adjusted for age, tumor stage and grade (Overall survival: HR = 0.53, 0.33-0.86, breast cancer-specific survival: HR = 0.26, 0.10-0.71, p = 0.009). A similar advantageous hazard ratio was found in users with ER positive, ER negative and HER2neu positive tumors. A similar significantly better survival was noted for colorectal cancer after adjustment for age, tumor stage and grade (Overall survival: HR = 0.53, 0.33-0.85, colorectal cancer-specific survival: HR = 0.44, 0.21-0.88, p = 0.02). Women who used bisphosphonates before diagnosis did not exhibit a significant survival benefit. Pharmacogenetic studies of F(D)PPS (Farnesyl Pyrophosphate Synthase), a gene coding a key step in the mevalonate pathway revealed direct correlation between a minor homozygous status and survival in bisphosphonate users. Conclusions The use of 2nd-generation bisphosphonates initiated after diagnosis was associated with a significant improvement in overall and in cancer-specific survival of postmenopausal women with breast or colon cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-03.
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