Risk of heart disease following treatment for breast cancer: results from a population-based cohort study

  1. Haomin Yang  Is a corresponding author
  2. Nirmala Bhoo Pathy
  3. Judith S Brand
  4. Elham Hedayati
  5. Felix Grassmann
  6. Erwei Zeng
  7. Jonas Bergh
  8. Weiwei Bian
  9. Jonas F Ludvigsson
  10. Per Hall
  11. Kamila Czene
  1. Fujian Medical University, China
  2. University of Malaya, Malaysia
  3. Örebro University, Sweden
  4. Karolinska Institutet, Sweden

Abstract

Background: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure and ischemic heart disease in women diagnosed with breast cancer.

Methods: A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001-2008 in the Stockholm-Gotland region and followed-up until 2017. Time-dependent risks of arrhythmia, heart failure and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.

Results: Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR=1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following loco-regional radiotherapy.

Conclusions: Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.

Funding: This work was supported by the Swedish Research Council [grant no: 2018-02547]; Swedish Cancer Society [grant no: CAN-19-0266] and FORTE [grant no: 2016-00081].

Data availability

The data used in this study are owned by the Swedish National Board of Health and Welfare and Statistics Sweden. According to Swedish law and GDPR, the authors are not able to make the dataset publicly available. Any researchers (including international researchers) interested in obtaining the data can do so by the following steps: 1) apply for ethical approval from their local ethical review boards; 2) contact the Swedish National Board of Health and Welfare and/or Statistics Sweden with the ethical approval and make a formal application of use of register data.

Article and author information

Author details

  1. Haomin Yang

    Department of Epidemiology and Health Statistics, Fujian Medical University, Fuzhou, China
    For correspondence
    haomin.yang@ki.se
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2252-2606
  2. Nirmala Bhoo Pathy

    Department of Social and Preventive Medicine, University of Malaya, Kuala Lumpur, Malaysia
    Competing interests
    Nirmala Bhoo Pathy, received educational grants to their institution from Novartis, Pfizer, AIA Bhd and Pharmaceutical Association of Malaysia.Has received speaker's fees from Novartis, Pfizer and Roche, and received travel support from Roche and Pharmaceutical Association of Malaysia to attend conferences in 2018 and 2019. Has served on the advisory board of Pfizer Asia Pacific, Malaysia (2017/18 year), and been a committee member for Together Against Cancer (NGO) (2018 and 2019). Roche Diagnostics also provided Nirmala Bhoo-Pathy with research material, namely COVID-19 total antibody kits. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0568-8863
  3. Judith S Brand

    School of Medical Sciences, Örebro University, Örebro, Sweden
    Competing interests
    No competing interests declared.
  4. Elham Hedayati

    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  5. Felix Grassmann

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1390-7528
  6. Erwei Zeng

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  7. Jonas Bergh

    Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    Jonas Bergh, research was supported by payments from Amgen, AstraZeneca, Bayer, Merck, Roche and Sanofi-Aventis to their institution, along with payments from non-profit organisations (Swedish Cancer Society and Knut Alice Wallenberg) and the Swedish Research Council. Also gave lectures to Astra Zeneca and Roche (no personal payment was received for these). Is a scientific advisor to The Medical product agency and to EMA, and is a representative of Swedish Breast Cancer Group. The author has no other competing interests to declare..
  8. Weiwei Bian

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  9. Jonas F Ludvigsson

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    Jonas F Ludvigsson, coordinates a study on behalf of the Swedish IBD quality register (SWIBREG). This study has received funding from Janssen corporation. The author has no other competing interests to declare..
  10. Per Hall

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5640-9126
  11. Kamila Czene

    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.

Funding

Natural Science Foundation of Fujian Province (2021J01721)

  • Haomin Yang

China Scholarship council

  • Weiwei Bian

Startup Fund for High-level Talents of Fujian Medical University (XRCZX2020007)

  • Haomin Yang

Startup Fund for Scientific Research, Fujian Medical University (2019QH1002)

  • Haomin Yang

Laboratory Construction Program of Fujian Medical University (1100160208)

  • Haomin Yang

Vetenskapsrådet (2018-02547)

  • Kamila Czene

Swedish Cancer Foundation (CAN-19-0266)

  • Kamila Czene

Forskningsrådet om Hälsa, Arbetsliv och Välfärd (2016-00081)

  • Kamila Czene

University of Malaya Impact-Oriented Interdisciplinary Research Grant Programme (IIRG006C-19HWB)

  • Nirmala Bhoo Pathy

China scholarship council

  • Erwei Zeng

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Wadih Arap, Rutgers Cancer Institute of New Jersey, United States

Ethics

Human subjects: The study was approved by the Regional Ethical Review Board in Stockholm (Dnr 2009/254-31/4). In accordance with their decision, it was not necessary to obtain informed consent from participants involved in the study. All individuals' information was anonymized and de-identified prior to analysis.

Version history

  1. Received: June 23, 2021
  2. Preprint posted: September 21, 2021 (view preprint)
  3. Accepted: March 8, 2022
  4. Accepted Manuscript published: March 16, 2022 (version 1)
  5. Version of Record published: March 22, 2022 (version 2)

Copyright

© 2022, Yang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Haomin Yang
  2. Nirmala Bhoo Pathy
  3. Judith S Brand
  4. Elham Hedayati
  5. Felix Grassmann
  6. Erwei Zeng
  7. Jonas Bergh
  8. Weiwei Bian
  9. Jonas F Ludvigsson
  10. Per Hall
  11. Kamila Czene
(2022)
Risk of heart disease following treatment for breast cancer: results from a population-based cohort study
eLife 11:e71562.
https://doi.org/10.7554/eLife.71562

Share this article

https://doi.org/10.7554/eLife.71562

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