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Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid.
JAMA Intern Med. 2014 Oct; 174(10):1550-7.JIM

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).

Authors+Show Affiliations

San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco2California Pacific Medical Center Research Institute, San Francisco.Center for Aging and Population Health, Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.Department of Medicine, University of Minnesota, Minneapolis.Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego.San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25111880

Citation

Hue, Trisha F., et al. "Effect of Bisphosphonate Use On Risk of Postmenopausal Breast Cancer: Results From the Randomized Clinical Trials of Alendronate and Zoledronic Acid." JAMA Internal Medicine, vol. 174, no. 10, 2014, pp. 1550-7.
Hue TF, Cummings SR, Cauley JA, et al. Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. JAMA Intern Med. 2014;174(10):1550-7.
Hue, T. F., Cummings, S. R., Cauley, J. A., Bauer, D. C., Ensrud, K. E., Barrett-Connor, E., & Black, D. M. (2014). Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. JAMA Internal Medicine, 174(10), 1550-7. https://doi.org/10.1001/jamainternmed.2014.3634
Hue TF, et al. Effect of Bisphosphonate Use On Risk of Postmenopausal Breast Cancer: Results From the Randomized Clinical Trials of Alendronate and Zoledronic Acid. JAMA Intern Med. 2014;174(10):1550-7. PubMed PMID: 25111880.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid. AU - Hue,Trisha F, AU - Cummings,Steven R, AU - Cauley,Jane A, AU - Bauer,Douglas C, AU - Ensrud,Kristine E, AU - Barrett-Connor,Elizabeth, AU - Black,Dennis M, PY - 2014/8/12/entrez PY - 2014/8/12/pubmed PY - 2015/1/31/medline SP - 1550 EP - 7 JF - JAMA internal medicine JO - JAMA Intern Med VL - 174 IS - 10 N2 - 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). SN - 2168-6114 UR - https://www.unboundmedicine.com/medline/citation/25111880/Effect_of_bisphosphonate_use_on_risk_of_postmenopausal_breast_cancer:_results_from_the_randomized_clinical_trials_of_alendronate_and_zoledronic_acid_ L2 - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/jamainternmed.2014.3634 DB - PRIME DP - Unbound Medicine ER -