Inflammatory Markers and Cardiovascular Disease in Breast Cancer Survivors

Background: Inflammation in breast cancer survivors (BCS) may play a role in developing cardiovascular disease (CVD). Prior studies have not included cancer-free comparison cohorts (CC) that can help elucidate if BCS have an increased risk of CVD. We evaluated whether incident CVD is greater in BCS compared with CC, and if the excess risk can be attributed to different levels of inflammatory markers, adjusting for pre-existing cardiovascular risk factors, demographic, and clinical characteristics. This preliminary analysis focuses on C-reactive protein (CRP), which has been strongly correlated with CVD. Methods: We conducted a prospective cohort study of 315 BC survivors aged 55-85 years and 321 CC from the KPSC health plan. Of these, 70% in each group (N=218 BCS, N=222 CC) agreed to blood draws for assessment of inflammatory markers at baseline and every 8 months until month 32. Participants were followed a maximum of 5 years or until a CVD event, death, or health plan disenrollment, whichever came first. Person-year (PY) rates for CV events were calculated by cumulative CRP levels over the 32 months. Bivariate and multivariable Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between cumulative CRP (using CVD risk-related cut points: <1.0 (low), 1.0-3.0 (moderate), and >3.0 mg/dL (high) and 5-year composite CV event. The association was also evaluated by cumulative CRP levels, with CC as the reference group. Multivariable models were adjusted for age, demographic characteristics, and cardiometabolic risk factors. Results: BCS had a higher crude CV event PY rate (33.3 per 1,000 PY) vs. CC (24.7 per 1,000 PY). In BCS, the 5-year CV event rate rose from 32.3 per 1,000 PY in the lowest CRP level (<1.0 mg/dL) to 34.4 per 1,000 PY (1.0-3.0 mg/dL), and then 40.8 per 1,000 PY (>3.0 mg/dL) (p-trend=0.68). Further, the CV event rates were greater in BCS than in CC in each of these CRP levels. In the crude model stratified by cohort, BCS with higher cumulative CRP levels had a greater CVD risk compared to those with normal CRP levels (HR>3.0 mg/dL=1.24, 95% CI: 0.45-3.43; HR1.0-3.0 mg/dL=1.05, 95% CI: 0.44-2.45), although results were not statistically significant. We observed similar trends in the CC. In the crude model stratified by CRP, BCS had a higher CVD risk than CC across all CRP categories, although the results were not significant (HRBCS CRP <1.0 mg/dL=1.36, 95% CI:0.53-3.46; HRBCS CRP 1.0-3.0 mg/dL=1.39, 95% CI: 0.49-3.91; HRBCS CRP >3.0 mg/dL=1.01, 95% CI:0.26-3.98). These risks attenuated in both multivariable models. Conclusions: Preliminary results signal higher cumulative CRP levels may differentially affect CVD risk in BCS than in CC, but larger studies are needed for confirmation. Further analyses will examine if other inflammatory markers (IL-6, Il-8, IL-10, and TNF) predict long-term CVD risk in BCS. Citation Format: Talar S. Habeshian, Michael R. Irwin, Lie H. Chen, Jiaxiao Shi, Richard Olmstead, Reina Haque. Role of inflammatory markers in the development of cardiovascular conditions in breast cancer survivors and matched comparison groups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2329.