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.
Reviewing Editor
- 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
- 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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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
Further reading
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- Cancer Biology
- Epidemiology and Global Health
Background:
Age is the most important risk factor for cancer, but aging rates are heterogeneous across individuals. We explored a new measure of aging-Phenotypic Age (PhenoAge)-in the risk prediction of site-specific and overall cancer.
Methods:
Using Cox regression models, we examined the association of Phenotypic Age Acceleration (PhenoAgeAccel) with cancer incidence by genetic risk group among 374,463 participants from the UK Biobank. We generated PhenoAge using chronological age and nine biomarkers, PhenoAgeAccel after subtracting the effect of chronological age by regression residual, and an incidence-weighted overall cancer polygenic risk score (CPRS) based on 20 cancer site-specific polygenic risk scores (PRSs).
Results:
Compared with biologically younger participants, those older had a significantly higher risk of overall cancer, with hazard ratios (HRs) of 1.22 (95% confidence interval, 1.18–1.27) in men, and 1.26 (1.22–1.31) in women, respectively. A joint effect of genetic risk and PhenoAgeAccel was observed on overall cancer risk, with HRs of 2.29 (2.10–2.51) for men and 1.94 (1.78–2.11) for women with high genetic risk and older PhenoAge compared with those with low genetic risk and younger PhenoAge. PhenoAgeAccel was negatively associated with the number of healthy lifestyle factors (Beta = –1.01 in men, p<0.001; Beta = –0.98 in women, p<0.001).
Conclusions:
Within and across genetic risk groups, older PhenoAge was consistently related to an increased risk of incident cancer with adjustment for chronological age and the aging process could be retarded by adherence to a healthy lifestyle.
Funding:
This work was supported by the National Natural Science Foundation of China (82230110, 82125033, 82388102 to GJ; 82273714 to MZ); and the Excellent Youth Foundation of Jiangsu Province (BK20220100 to MZ).
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
