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Risk of breast cancer among patients with bioprosthetic or mechanical valve replacement: a population-based study in Sweden

  • Epidemiology
  • Published:
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Abstract

The association between breast cancer and warfarin is inconclusive as most previous studies examined their association using patients with thromboembolism, whereas thromboembolism itself is a risk factor for cancer. We explored this issue using patients received mechanical heart valves replacement as a proxy for warfarin exposure as these patients need a lifelong warfarin treatment, and compared them with patients received bioprosthesis valves replacement (short-term warfarin treatment) in Sweden between 1987 and 2010. Patients who were operated on for valve replacement were identified from the Swedish Hospital Discharge Registry and linked to the Swedish Cancer Registry to examine the hazard ratios of subsequent breast cancer. A total of 12,242 women were operated on for valve replacement (5481 with mechanical valve and 6401 with bioprosthetic valve). For the entire cohort, the HR of breast cancer was 1.49 (95 % CI 1.09–2.02) among patients with mechanical valve replacement compared to those with bioprosthetic valve replacement. After controlling for a number of confounding factors using propensity score weighting, the HR was 1.69 (95 % CI 1.15–2.47). Our study found that patients with mechanical valve replacement have an increased risk of breast cancer compared to those with bioprosthetic valve replacement. If confirmed, this increased risk should be considered when recommending breast cancer screening for women with mechanical valve replacement. Long-term use of warfarin may explain the observed increase. If so, patients who have used warfarin long-term for other reasons should be studied for a possible increased risk of breast cancer.

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Acknowledgments

The authors wish to thank the CPF’s Science Editors Stephen Gilliver and Patrick Reilly for their valuable comments on the text.

Author contribution

JJ, BZ, KS, RH, AF, and JS were responsible for the study concept and design. JS obtained funding. KS and JS acquired the data. JJ analyzed and interpreted the data. JJ did the statistical analysis. JJ drafted the manuscript, and all authors revised it for important intellectual content.

Funding

This work was supported by grants to Dr Kristina Sundquist from the Swedish Research Council (K2009-70X-15428-05-3; K2012-70X-15428-08-3), grants to Bengt Zöller from the Swedish Heart–Lung Foundation, and VR (K2015-65X-22660-01-3) as well as ALF funding from Region Skåne awarded to Jan Sundquist, Kristina Sundquist, Bengt Zöller, and Dr Jianguang Ji. The funding agencies had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. The researchers were independent of the funding agencies.

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Authors and Affiliations

  1. Center for Primary Health Care Research, CRC, Lund University/Region Skåne, Skåne University Hospital, Building 28, Floor 11, Jan Waldenströms gata 35, 205 02, Malmö, Sweden

    Jianguang Ji, Bengt Zöller, Jan Sundquist & Kristina Sundquist

  2. Stanford Prevention Research Center, Stanford University, Stanford, CA, USA

    Amato Giaccia, Robert Haile, Jan Sundquist & Kristina Sundquist

Authors
  1. Jianguang Ji
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  2. Bengt Zöller
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  3. Amato Giaccia
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  4. Robert Haile
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  5. Jan Sundquist
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  6. Kristina Sundquist
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Corresponding author

Correspondence to Jianguang Ji.

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Ethical approval

This study was approved by the Regional Ethical Review Board of Lund University in Sweden.

The novelty and impact statements

Patients with mechanical valve replacement have an increased risk of breast cancer compared to those with bioprosthetic valve replacement. Long-term use of warfarin may explain the observed increase.

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Ji, J., Zöller, B., Giaccia, A. et al. Risk of breast cancer among patients with bioprosthetic or mechanical valve replacement: a population-based study in Sweden. Breast Cancer Res Treat 154, 369–375 (2015). https://doi.org/10.1007/s10549-015-3607-9

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  • DOI: https://doi.org/10.1007/s10549-015-3607-9

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