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Associations between diabetes medication use and risk of second breast cancer events and mortality

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Abstract

Purpose

Diabetes and certain diabetes medications have been shown to influence breast cancer (BC) risk. Less is known about their relation to BC outcomes. Our objective was to evaluate the effects of diabetes and diabetes medications on risk of second breast cancer events (SBCE) and mortality.

Methods

This population-based cohort study was conducted among women diagnosed with early-stage (I–II) BC and enrolled in an integrated health plan. Exposures of interest were diabetes and medication classes including insulin, metformin, and sulfonylureas. Outcomes of interest were SBCE defined as recurrence or second primary BC, BC-specific mortality, and all-cause mortality. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for diabetes and medication use while accounting for potential confounders and competing risks.

Results

Among 4,216 women, 13 % developed SBCE during a median follow-up of 6.3 years. 610 women had diabetes of which 76 % used oral diabetes medication and/or insulin. Findings suggested that diabetes increased the risk of recurrence (HR = 1.57; 95 % CI 1.09–2.25) but not overall SBCE (HR = 1.29; 95 % CI 0.94–1.76) or second primary BC (HR = 0.74; 95 % CI 0.39–1.41). Among women with diabetes, insulin use was associated with increased risks of recurrence (HR = 1.94; 95 % CI 1.08–3.48) and all-cause mortality (HR = 2.33; 95 % CI 1.70–3.20). Metformin use was associated with lower all-cause mortality (HR = 0.55; 95 % CI 0.38–0.79).

Conclusions

Our findings show an association between diabetes and increased recurrence risk, and risk may be greater among insulin users. Metformin may reduce all-cause mortality among BC survivors. Given the growing breast cancer survivor population, further research in larger, more diverse populations is warranted.

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Acknowledgments

This manuscript was supported by a Grant from the National Cancer Institute (R01 CA120562 to D.M.B.) at Group Health Research Institute. Collection of cancer incidence data used in this study was supported by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center (N01-CN-67009 and N01-PC-35142) from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute with additional support from the State of Washington. The National Institutes of Health Cancer Prevention Training Grant in Nutrition, Exercise and Genetics (R25 CA094880) at the University of Washington supported author G.S.C. Results from this study were presented, in part, at the 47th annual meeting of the Society for Epidemiologic Research in a Concurrent Contributed Session, Seattle, WA, June 24–27, 2014.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Center for Pharmacoepidemiology and Pharmacoeconomic Research, University of Illinois at Chicago, 833 South Wood Street M/C 871, Chicago, IL, 60612, USA

    Gregory S. Calip

  2. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North M4-B402, Seattle, WA, 98109, USA

    Gregory S. Calip

  3. Department of Epidemiology, University of Washington, 1959 Northeast Pacific Street F-262, Seattle, WA, 98195, USA

    Gregory S. Calip & Denise M. Boudreau

  4. Group Health Research Institute, 1730 Minor Avenue Suite 1600, Seattle, WA, 98101, USA

    Onchee Yu & Denise M. Boudreau

  5. Division of Hematology/Oncology, University of Illinois at Chicago, 840 South Wood Street M/C 713, Chicago, IL, 60612, USA

    Kent F. Hoskins

  6. School of Pharmacy, University of Washington, 1959 Northeast Pacific Street H-364, Seattle, WA, 98195, USA

    Denise M. Boudreau

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  1. Gregory S. Calip
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  2. Onchee Yu
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Correspondence to Gregory S. Calip.

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Calip, G.S., Yu, O., Hoskins, K.F. et al. Associations between diabetes medication use and risk of second breast cancer events and mortality. Cancer Causes Control 26, 1065–1077 (2015). https://doi.org/10.1007/s10552-015-0599-z

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