Racial and ethnic differences in cardiovascular disease mortality among women diagnosed with ductal carcinoma in situ in the United States

Background: Ductal carcinoma in situ (DCIS) is associated with an elevated risk of cardiovascular disease (CVD) mortality, which may be due to comorbidities or cancer treatment, yet prior studies examining racial and ethnic differences are limited. The aim of this study is to investigate the association between race, ethnicity and CVD mortality among women diagnosed with DCIS in the United States. Methods: We included women diagnosed with a first primary DCIS aged 20-84 between 2000 to 2017 in the U.S. Surveillance, Epidemiology, and End Results, and followed for more than one year. Fine and Gray regression was used to estimate sub-distribution hazard ratios (HRs) for CVD mortality by race and ethnicity (Hispanic, non-Hispanic Asian American (NH-AA), NH-Black, NH-Native Hawaiian and other Pacific Islander (NH-NHPI), and NH-White), adjusting for age at diagnosis, year of diagnosis, surgery type, and radiotherapy, and accounting for competing risks of non-CVD death. Models were further stratified by DCIS diagnosis age (<50 and ≥ 50) and year (2000-2004, 2005-2009, and 2010-2017). Cumulative incidence of CVD mortality was also assessed by race and ethnicity, accounting for competing risks. Results: Among 158,072 women diagnosed with DCIS (median follow-up=6.80 years; mean age=58.47 years), 4,504 CVD deaths were identified (3,190 heart disease, 964 cerebrovascular disease, and 350 other CVD deaths). Compared to NH-White women, NH-Black and NH-NHPI women had a higher risk of CVD mortality (HR NH-Black = 1.61, 95%CI=1.48-1.76; HR NH-NHPI = 1.80, 95%CI=1.22-2.65) while NH-AA women had a lower risk of CVD mortality (HR NH-AA = 0.68, 95%CI=0.60-0.79). There was no significant association of CVD mortality for Hispanic women compared NH-White women (HR Hispanic = 0.91, 95%CI=0.80-1.03). Although the increased risk of CVD mortality remained higher in NH-Black and NH-NHPI women regardless of age at DCIS diagnosis, younger women (<50 years) had greater relative risk compared to older women (≥50 years) in stratified analyses (HR NH-Black, <50 = 3.93, 95%CI=2.62-5.90, HR NH-Black, ≥50 = 1.56, 95%CI=1.43-1.71; HR NH-NHPI,<50 = 4.19, 95%CI=1.04-16.97, HR NH-NHPI, ≥50 = 1.73, 95%CI=1.16-2.59). Risk of CVD mortality increased by year of diagnosis, especially among NH-Black and NH-NHPI women. NH-Black and NH-NHPI women had the highest cumulative incidence of CVD mortality at 5-years (1.51%, 95%CI=1.33%-1.72% and 1.53% 95%CI=0.81%-2.66% respectively) and 10-years (4.29%, 95%CI=3.90%-4.70% and 4.17% 95%CI=2.62%-6.26% respectively) post DCIS diagnosis. Conclusions: NH-Black and NH-NHPI women diagnosed with DCIS had higher CVD mortality compared to NH-White women, especially among younger women and those diagnosed in recent years. Further studies are needed to understand multi-level factors driving the increased risk of CVD mortality in NH-Black and NH-NHPI women with DCIS.