Risk of heart disease following treatment for breast cancer: results from a population-based cohort study
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
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.
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.
Reviewing Editor
- Wadih Arap, Rutgers Cancer Institute of New Jersey, United States
Version history
- Received: June 23, 2021
- Preprint posted: September 21, 2021 (view preprint)
- Accepted: March 8, 2022
- Accepted Manuscript published: March 16, 2022 (version 1)
- 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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Further reading
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- Epidemiology and Global Health
The NIH-funded RECOVER study is collecting clinical data on patients who experience a SARS-CoV-2 infection. As patient representatives of the RECOVER Initiative’s Mechanistic Pathways task force, we offer our perspectives on patient motivations for partnering with researchers to obtain results from mechanistic studies. We emphasize the challenges of balancing urgency with scientific rigor. We recognize the importance of such partnerships in addressing post-acute sequelae of SARS-CoV-2 infection (PASC), which includes ‘long COVID,’ through contrasting objective and subjective narratives. Long COVID’s prevalence served as a call to action for patients like us to become actively involved in efforts to understand our condition. Patient-centered and patient-partnered research informs the balance between urgency and robust mechanistic research. Results from collaborating on protocol design, diverse patient inclusion, and awareness of community concerns establish a new precedent in biomedical research study design. With a public health matter as pressing as the long-term complications that can emerge after SARS-CoV-2 infection, considerate and equitable stakeholder involvement is essential to guiding seminal research. Discussions in the RECOVER Mechanistic Pathways task force gave rise to this commentary as well as other review articles on the current scientific understanding of PASC mechanisms.
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- Epidemiology and Global Health
Background:
In most of the world, the mammography screening programmes were paused at the start of the pandemic, whilst mammography screening continued in Denmark. We examined the mammography screening participation during the COVID-19 pandemic in Denmark.
Methods:
The study population comprised all women aged 50–69 years old invited to participate in mammography screening from 2016 to 2021 in Denmark based on data from the Danish Quality Database for Mammography Screening in combination with population-based registries. Using a generalised linear model, we estimated prevalence ratios (PRs) and 95% confidence intervals (CIs) of mammography screening participation within 90, 180, and 365 d since invitation during the pandemic in comparison with the previous years adjusting for age, year and month of invitation.
Results:
The study comprised 1,828,791 invitations among 847,766 women. Before the pandemic, 80.2% of invitations resulted in participation in mammography screening within 90 d, 82.7% within 180 d, and 83.1% within 365 d. At the start of the pandemic, the participation in screening within 90 d was reduced to 69.9% for those invited in pre-lockdown and to 76.5% for those invited in first lockdown. Extending the length of follow-up time to 365 d only a minor overall reduction was observed (PR = 0.94; 95% CI: 0.93–0.95 in pre-lockdown and PR = 0.97; 95% CI: 0.96–0.97 in first lockdown). A lower participation was, however, seen among immigrants and among women with a low income.
Conclusions:
The short-term participation in mammography screening was reduced at the start of the pandemic, whilst only a minor reduction in the overall participation was observed with longer follow-up time, indicating that women postponed screening. Some groups of women, nonetheless, had a lower participation, indicating that the social inequity in screening participation was exacerbated during the pandemic.
Funding:
The study was funded by the Danish Cancer Society Scientific Committee (grant number R321-A17417) and the Danish regions.