Risk of heart disease following treatment for breast cancer: results from a population-based cohort study
- Fujian Medical University, China
- University of Malaya, Malaysia
- Örebro University, Sweden
- 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
Nirmala Bhoo Pathy
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.
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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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
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Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).
Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.
Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
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