Association of Early-Stage Breast Cancer and Subsequent Chemotherapy With Risk of Atrial Fibrillation
Bibliographic record
Abstract
Importance: Several types of cancer have been linked to a higher risk of developing atrial fibrillation (AF). Fewer data exist regarding early-stage breast cancer (EBC), for which cardio-oncology concerns are more pertinent. Objective: To investigate the association of EBC and subsequent chemotherapy with the risk of developing AF. Design, Setting, and Participants: This was a population-based, retrospective, matched cohort study conducted in Toronto, Ontario, Canada, of 68 113 women diagnosed with EBC between April 2007 and December 2016 who were matched 1:3 to a cancer-free control group based on birth year and receipt of breast imaging. Prevalence of AF before the index date (date of EBC diagnosis) was compared between the cohorts using the McNemar test. Cumulative incidence function curves were used to describe the AF incidence. To study preexisting AF, participants were matched before exclusion for prior AF. For the remaining analyses, we excluded women with prior AF before matching. An analysis was conducted beginning 1 year after the index date (ie, excluding AF diagnoses in year 1), which we stratified by chemotherapy exposure. Multivariable cause-specific regression was used to determine the hazard ratio (HR) associated with EBC relative to the controls and the association of chemotherapy with AF in patients with EBC. Exposures: Breast cancer and chemotherapy. Main Outcomes and Measures: Incidence of AF. Results: A total of 68 113 women with EBC and 204 330 cancer-free controls were included in the study; both groups had a mean (SD) age of 60 (13) years. Of the women with EBC, 44.3% were diagnosed as having stage I breast cancer; 38.7%, stage II; and 13.4%, stage III; cancer stage information was missing for 3.6% of the patients. No difference was observed in preexisting AF prevalence (5.3% in the EBC cohort vs 5.2% in controls; P = .21). At 10 years after the index date, the AF incidence was 7.4% (95% CI, 7.1%-7.7%) for women with EBC and 6.8% (95% CI, 6.7%-7.0%) for the controls (P < .001). The adjusted cause-specific HR was significantly elevated at year 1 (HR, 2.16; 95% CI, 1.94-2.41) and after year 5 (HR, 1.20; 95% CI, 1.11-1.30) but not during years 2 through 5. Analyses beginning 1 year after diagnosis showed attenuated differences that remained statistically significant: the cumulative incidence of AF at 9-year follow-up was 7.0% (95% CI, 6.7%-7.3%) for patients with EBC and 6.5% (95% CI, 6.3%-6.7%) for the cancer-free controls. The rate of AF was higher in women who received chemotherapy (adjusted HR, 1.23; 95% CI, 1.13-1.35) but was not associated with exposure to anthracyclines or trastuzumab. Conclusions and Relevance: This study's findings suggest that patients with EBC may not have a higher prevalence of AF before cancer diagnosis. A higher rate of AF was observed in the first year and after 5 years following the EBC diagnosis. The rate of AF was higher in patients who received chemotherapy but appeared to not be associated with specific cardiotoxic agents. These findings suggest that the early and late periods of increased AF risk in EBC survivors warrant focused research to better understand the underlying causes and subsequent implications.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".