Abstract 4365249: Treatment Modality and Cardiovascular Mortality in Breast Cancer: A SEER and Single-Center Analysis by Stage and Receptor Subtype

Background: CV mortality (CVM) is a critical competing risk in breast cancer (BC). How therapy type affects CVM by stage and receptor subtype remains incompletely defined. Objective: Compare CVM risk across treatment modalities: chemotherapy alone (C), radiotherapy alone (R), or both (C + R), in BC stages I–IV (2010–2015), stratified by receptor subtype (Luminal A (LA), Luminal B (LB), Her2-enriched, triple negative BC (TNBC)). Methods: Among 282,991 SEER patients (2010–2015), multivariable Cox models (adjusted for age, race, and laterality) and stratified by stage and receptor status estimated adjusted hazard ratios (AHRs) for CVM: C vs R and C + R vs R. Receptor-specific temporal CVM trends are shown in Figure 1. To account for baseline CV comorbidity, 1555 patients from Georgia Cancer Center (2010–2015) were analyzed, adjusting for age, receptor status, stage, hypertension, diabetes, and hyperlipidemia. Results: For the SEER cohort, there was an overall downward trend of CVm across stages 1, 2, and 3. In stage II breast cancer, both LA and LB subtypes showed significant reductions in cardiovascular mortality with C or C + R compared to R. For LA, the AHR was 0.75 (95% CI: 0.59–0.95) for C vs R and 0.75 (95% CI: 0.61–0.93) for C + R vs R. For LB, AHRs were 0.54 (95% CI: 0.33–0.90) for C vs R and 0.44 (95% CI: 0.27–0.74) for C + R vs R. In stage III disease, patients with LA who received C + R had a significantly lower risk (AHR 0.49, 95% CI: 0.35–0.68), as did those with TNBC receiving C + R (AHR 0.33, 95% CI: 0.13–0.82). There were no significant associations for other stage-receptor subgroups (p > 0.05). In the Georgia cohort, neither C nor C + R was associated with lower cardiovascular mortality compared to R (p > 0.05). Conclusions: In stages I–III, Patients selected to receive C (± R) has lower CVM vs R alone in LA (stage II–III), LB (stage II), and TNBC (stage III). CVM did not decline in stage IV (AHR ~1.0), possibly due to expanding use of newer systemic therapies. Temporal trend analysis (Figure 1) suggests broader improvements in CV risk management perhaps due to improvement of cardiac care of BC patients; aligning FDA approval timelines with CVM in BC may further elucidate therapy-related CV risks.