Cardiovascular mortality among cancer survivors who developed breast cancer as a second primary malignancy

• Background: Patients with breast cancer are at increased risk of cardiovascular diseases and cardiovascular mortality, potentially due to treatment-related cardiotoxicity, early menopause, and psychological distress. Cancer survivors who developed breast cancer as a second malignancy (BCa-2) are common and may experience cancer treatment and distress for a second time. It is however unknown whether BCa-2 patients have increased risk of cardiovascular mortality compared to patients with breast cancer as the first malignancy (BCa-1) and the cancer-free female population.Methods: Using the Surveillance, Epidemiology, and End Results database, we conducted a cohort study including 1,024,047 patients with BCa-1 and 41,744 with BCa-2 diagnosed at age of 30 years and older during 1975-2016, and the corresponding female population of 994,415,911 person-years in the U.S.. Compared with patients with BCa-1 and the general population, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among patients with BCa-2 by using multivariable Poisson regression.Results: During the median follow-up of 5.9 years (interquartile range, 2.4-11.3 years), 3,550 and 71,298 cardiovascular deaths were observed in BCa-2 and BCa-1 patients. Overall, BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the general population (IRR 1.07, 95% CI 1.03-1.10) and BCa-1 patients (IRR 1.13, 95% CI 1.10-1.17) with the adjustment of demographic factors. When comparing BCa-2 with BCa-1, the association was further independent of tumor characteristics and treatment modes (IRR 1.15, 95% CI 1.11-1.19). The elevated risk of cardiovascular mortality was mostly pronounced at age of follow-up between 30 and 79 years (IRR 1.31, 95% CI 1.23-1.40 compared with the general population; IRR 1.34, 95% CI 1.25-1.43 compared with BCa-1), whereas the risk was mildly increased, if any, at age of 80+ years compared with BCa-1 (IRR 1.07, 95% CI 1.02-1.11). The increased risk at age of 30-79 years in BCa-2 was particularly greater within the first month after cancer diagnosis compared with the general population (IRR 3.20, 95% CI 2.34-4.38). In contrast, cardiovascular mortality rate in BCa-2 was comparable to that in BCa-1 within the first month (IRR 0.87, 95% CI 0.63-1.21).Conclusions: Our findings suggest that patients with BCa-2, particularly in patients younger than 80 years, are at increased risk of cardiovascular mortality, compared with the general population and patients with BCa-1.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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