Chengshi Wang1,2, Kejia Hu3, Chuanxu Luo1, Lei Deng4, Katja Fall5, Rulla M Tamimi6,7, Unnur A Valdimarsdóttir6,8,9, Fang Fang3, Donghao Lu10,11,12. 1. Laboratory of Molecular Diagnosis of Cancer, and Department of Medical Oncology, Clinical Research Center for Breast Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China. 2. Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. 3. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. 4. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA. 5. Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, 701 85, Örebro, Sweden. 6. Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA. 7. Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA. 8. Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Sturlugata 8, 101, Reykjavik, Iceland. 9. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12a, 171 77, Solna, Sweden. 10. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. donghao.lu@ki.se. 11. Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, USA. donghao.lu@ki.se. 12. West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China. donghao.lu@ki.se.
Abstract
BACKGROUND: To assess the risk of cardiovascular mortality among cancer survivors who developed breast cancer as a second malignancy (BCa-2) compared with patients with first primary breast cancer (BCa-1) and the general population. METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 1,024,047 BCa-1 and 41,744 BCa-2 patients diagnosed from the age 30 between 1975 and 2016, and the corresponding US female population (994,415,911 person-years; 5,403,551 cardiovascular deaths). Compared with the general population and BCa-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among BCa-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among BCa-2 patients who died from cardiovascular disease. RESULTS: Although BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the population (IRR 1.08) and BCa-1 patients (IRR 1.15), the association was pronounced among individuals aged 30-49 years (BCa-2 vs. population: IRR 6.61; BCa-2 vs. BCa-1: IRR 3.03). The risk elevation was greatest within the first month after diagnosis, compared with the population, but comparable with BCa-1 patients. The case-crossover analysis confirmed these results. CONCLUSION: Our findings suggest that patients with BCa-2 are at increased risk of cardiovascular mortality.
BACKGROUND: To assess the risk of cardiovascular mortality among cancer survivors who developed breast cancer as a second malignancy (BCa-2) compared with patients with first primary breast cancer (BCa-1) and the general population. METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 1,024,047 BCa-1 and 41,744 BCa-2 patients diagnosed from the age 30 between 1975 and 2016, and the corresponding US female population (994,415,911 person-years; 5,403,551 cardiovascular deaths). Compared with the general population and BCa-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among BCa-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among BCa-2 patients who died from cardiovascular disease. RESULTS: Although BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the population (IRR 1.08) and BCa-1 patients (IRR 1.15), the association was pronounced among individuals aged 30-49 years (BCa-2 vs. population: IRR 6.61; BCa-2 vs. BCa-1: IRR 3.03). The risk elevation was greatest within the first month after diagnosis, compared with the population, but comparable with BCa-1 patients. The case-crossover analysis confirmed these results. CONCLUSION: Our findings suggest that patients with BCa-2 are at increased risk of cardiovascular mortality.
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