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Background: Cardiovascular disease (CVD) is associated with higher rates of incident cancer. Data are scarce regarding the association of incident CVD with oncologic outcomes after a cancer diagnosis., Objectives: This study sought to determine whether incident myocardial infarction (MI) or heart failure (HF) in breast cancer survivors is associated with oncologic outcomes., Methods: This was a population-based cohort study in Ontario, Canada, using linked administrative data sets of women diagnosed with first breast cancer between April 1, 2007, and March 31, 2015. A landmark analysis was conducted of women alive 2 years after breast cancer diagnosis, aged ≥40 years, and with available staging data and without recurrent/distant disease or preceding CVD. The exposure was a composite of MI and/or HF after the landmark date. The outcomes were cancer mortality, new non-breast malignancy diagnosis, and new chemotherapy initiation. Multivariable cause-specific hazards regression was used to determine the association of incident MI/HF (time-varying exposure) with outcomes., Results: A total of 30,694 women (median age of 60 years) were included, of whom 1,346 developed incident MI/HF at a median of 3.9 years after the landmark date. At 5 years, the cumulative incidence was 5.9% (95% CI: 5.6%-6.1%) for cancer death, 4.3% (95% CI: 4.1%-4.6%) for non-breast malignancy, and 25.7% (95% CI: 25.2%-26.2%) for new chemotherapy. Incident MI/HF was associated with a higher hazard of cancer death (HR: 3.94; 95% CI: 3.38-4.59), non-breast malignancy (HR: 1.39; 95% CI: 1.06-1.82), and new chemotherapy (HR: 1.25; 95% CI: 1.02-1.53)., Conclusions: Incident MI and/or HF after breast cancer treatment are associated with higher hazards of adverse oncologic outcomes, highlighting the need to prioritize care for these patients., Competing Interests: This work was funded by the Ted Rogers Program in Cardiotoxicity Prevention and the Early Career Women’s Heart and Brain Health Chair (from the Heart and Stroke Foundation of Canada and Canadian Institutes of Health Research) to Dr Abdel-Qadir. Dr Abdel-Qadir was funded by the National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Thavendiranathan (147814) was supported by a Canada Research Chair in Cardiooncology (CRC-2019-00097) and the Canadian Cancer Society/Canadian Institutes of Health Research’s W. David Hargraft Grant. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario Ministry of Health Postal Code Conversion File, which contains data copied under license from Canada Post Corporation and Statistics Canada. Parts of this material are based on data and/or information compiled and provided by the MOH, CIHI, and OH. Parts of this report are based on Ontario Registrar General (ORG) information on deaths, the original source of which is ServiceOntario. The views expressed therein are those of the author and do not necessarily reflect those of ORG or the Ministry of Public and Business Service Delivery. The analyses, conclusions, opinions and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. Dr Thavendiranathan has received consultation and speaker honoraria from Amgen, Boehringer Ingelheim, General Electric, and Takeda. Dr Amir has received honoraria from Sandoz and Seagen; and has provided consulting to AstraZeneca and Novartis. Dr Lee is the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. Dr Abdel-Qadir has received consultation and speaker honoraria from Amgen, AstraZeneca and Jazz Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel cardiovascular disease (CVD) risk factor in individuals without acute myeloid leukemia (AML)., Objectives: The aim of this study was to examine the association between mutations associated with CHIP (CHIP-related mutations) identified in patients at AML diagnosis and the risk for cardiovascular events (CVEs)., Methods: This was a retrospective cohort study of 623 patients with AML treated between 2015 and 2018 who underwent DNA analysis. Cause-specific hazard regression models were used to study the associations between pathogenic mutations in common CHIP-related genes ( DNMT3A , TET2 , ASXL1 , JAK2 , TP53 , SRSF2 , and SF3B1 ) and the rate of CVEs (heart failure hospitalization, acute coronary syndrome, coronary artery revascularization, ischemic stroke, venous thromboembolism, and CVD death) and between CVE development and all-cause mortality., Results: Patients were 64.6 ± 15.3 years of age, 265 (42.5%) were women, and 63% had at least 1 CHIP-related mutation. Those with CHIP-related mutations were older (69.2 ± 12.3 vs 56.6 ± 16.6 years; P  < 0.001) and had a greater prevalence of CVD risk factors and CVD history. In adjusted analysis, the presence of any CHIP-related mutation was associated with a higher rate of CVEs (HR: 1.74; 95% CI: 1.03-2.93; P  = 0.037) among intensively treated patients (anthracycline based) but not the whole cohort (HR: 1.26; 95% CI: 0.81-1.97; P  = 0.31). TP53 (HR: 4.18; 95% CI: 2.07-8.47; P < 0.001) and ASXL1 (HR: 2.37; 95% CI: 1.21-4.63; P  = 0.012) mutations were associated with CVEs among intensively treated patients. Interval development of CVEs was associated with all-cause mortality (HR: 1.99; 95% CI: 1.45-2.73; P  < 0.001)., Conclusions: Among patients with AML treated with intensive chemotherapy, mutations in CHIP-related genes were associated with an increased risk for developing incident CVEs after AML diagnosis., Competing Interests: This study was supported by the Ontario Early Research Award. Dr Calvillo-Argüelles is supported by the Hold ’em for Life Oncology Clinician Scientist Award at the University of Toronto’s Faculty of Medicine. Dr Thavendiranathan is supported by the Canadian Institutes of Health Research New Investigator Award (147814) and a Canada Research Chair in Cardio-Oncology. Dr Abdel-Qadir is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada. Dr Schimmer is supported by the Canadian Institutes of Health Research, the Canadian Cancer Society, and the Ontario Institute of Cancer Research with funding provided by the Ontario Ministry of Research and Innovation, the Princess Margaret Cancer Centre Foundation, and the Ministry of Long Term Health and Planning in the Province of Ontario; and holds the Ronald N. Buick Chair in Oncology Research. Dr Natarajan is supported by grants from the National Heart, Lung, and Blood Institute (R01HL142711, R01HL148050, R01HL151283, and R01HL148565) and Fondation Leducq (TNE-18CVD04). Dr Thavendiranathan has received honoraria from BI, Takeda, and Amgen. Dr. Schuh has received honoraria from Takeda, Novartis, Jazz, and Otsuka Pharmaceuticals; has received research support from Medivir and Takeda; and owns stock in AbbVie Pharmaceuticals. Dr. Schimmer is named as an inventor on patent applications related to the use of double-negative T cells in AML and cancer. Dr Gupta has received honoraria from Novartis, Bristol Myers Squibb Celgene, Pfizer, and Sierra Oncology. Dr Abdel-Qadir has received honoraria from Amgen. Dr Yee has received honoraria from Celgene/Bristol Myers Squibb, Roche, Takeda, Pfizer, TaiHo and Novartis; and has received research funding from Astex, Forma Therapeutics, Jazz, Janssen, Onconova, Medimmune, Genenetch, and Tolero Pharmaceuticals. Dr Natarajan has received grant support from Amgen, AstraZeneca, Boston Scientific, Apple, and Novartis; has received personal fees from AstraZeneca, Apple, Genentech, Novartis, Blackstone Life Sciences, and Foresite Labs; and reports spousal employment at Vertex, all unrelated to the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)