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JAMA Intern Med. 2014 Oct;174(10):1550-7. doi: 10.1001/jamainternmed.2014.3634.

Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid.

Author information

1
San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco.
2
San Francisco Coordinating Center, Department of Epidemiology and Biostatistics, University of California, San Francisco2California Pacific Medical Center Research Institute, San Francisco.
3
Center for Aging and Population Health, Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
4
Department of Medicine, University of Minnesota, Minneapolis.
5
Division of Epidemiology, Department of Family and Preventive Medicine, University of California, San Diego.

Erratum in

  • JAMA Intern Med. 2014 Nov;174(11):1875.

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).

PMID:
25111880
PMCID:
PMC4398333
DOI:
10.1001/jamainternmed.2014.3634
[Indexed for MEDLINE]
Free PMC Article

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