Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid
Trisha F Hue, Steven R Cummings, Jane A Cauley, Douglas C Bauer, Kristine E Ensrud, Elizabeth Barrett-Connor, Dennis M Black, Trisha F Hue, Steven R Cummings, Jane A Cauley, Douglas C Bauer, Kristine E Ensrud, Elizabeth Barrett-Connor, Dennis M Black
Abstract
Importance: Studies have shown that bisphosphonates may have antitumor and antimetastatic properties. Recently, observational studies have suggested a possible protective effect of bisphosphonates on breast cancer, but the effect of bisphosphonate use on risk of breast cancer has not been tested in randomized trials.
Objective: To assess the relationship of postmenopausal breast cancer incidence and bisphosphonate use using data from 2 randomized (1:1), double-blind, placebo-controlled trials.
Design, setting, and participants: The Fracture Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data were collected at clinical centers in the United States (FIT and HORIZON-PFT) and in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT). Women, in either study, with recurrent breast cancer or who reported a history of breast cancer were excluded from analyses. In each trial, a blinded review was conducted of each cancer adverse event report to verify incident invasive breast cancer cases. The primary analysis compared events in the active vs placebo group using a log-rank test.
Intervention: Alendronate vs placebo (FIT) or zoledronic acid vs placebo (HORIZON-PFT).
Main outcomes and measures: Hazard ratio for incident breast cancer in the bisphosphonate treatment group compared to the placebo group.
Results: There was no significant difference in the rate of breast cancer in FIT: 1.5% (n = 46) in the placebo group and 1.8% (n = 57) in the alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT, there was also no significant difference: 0.8% (n = 29) in the placebo group and 0.9% (n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There was also no significant difference when the data from FIT and HORIZON-PFT were pooled (HR, 1.20 [95% CI, 0.89-1.63]).
Conclusions and relevance: These 2 randomized clinical trials do not support the findings from observational research. Contrary to the results from observational studies, we found that 3 to 4 years of bisphosphonate treatment did not decrease the risk of invasive postmenopausal breast cancer.
Trial registration: clinicaltrials.gov Identifier: NCT00049829 (HORIZON-PFT).
Conflict of interest statement
Conflict of Interest Disclosures: Dr Ensrud serves as a consultant on a data monitoring committee for Merck Sharp & Dohme. No other disclosures are reported.
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Source: PubMed