Understanding competing mortality in patients with early-stage ER+ breast cancer.

Abstract

217 Background: Long-term endocrine therapy reduces recurrence in early-stage hormone receptor-positive breast cancer (BC) but may worsen comorbidities and survival. Understanding competing causes of mortality is essential for individualized treatment. We characterized cause-specific mortality and risk factor profiles for BC versus non-cancer death in early-stage estrogen receptor-positive (ER+) BC. Methods: This retrospective cohort study included patients treated with curative intent for Stage I-III ER+ BC from 2008-2017. Patient and disease characteristics were collected, and cause of death was classified as BC, cardiovascular disease (CVD), other cancer, or other causes. Using competing risk methods, cumulative incidence functions (CIF) were estimated at 5 and 10 years, overall and stratified by stage. Multivariable Cox models identified factors independently associated with cause of death. Results: Among 16,071 BC patients (mean age 61.9 years), 3,376 deaths occurred. At 10 years, CVD was the leading cause of death overall (CIF 5.9%; 95% CI, 5.6%–6.3%), followed by BC (5.5%; 95% CI, 5.1%–5.8%), other causes (5.0%; 95% CI, 4.7%–5.4%), and other cancers (2.8%; 95% CI, 2.5%–3.1%). CV mortality exceeded BC mortality in Stage I at 5 years (2.1% vs. 0.72%) and 10 years (5.5% vs. 2.1%), while BC was the leading cause of death in Stage III (10-year CIF: 21% vs. 7.9% for CVD). In multivariable models, BC death was associated with higher stage (Stage III: adjusted HR 12.1; 95% CI, 10.1–14.5), Black non-Hispanic race (HR 1.41; 95% CI, 1.11–1.79), and Medicare insurance (HR 1.57; 95% CI, 1.26–1.95). Death from other causes was associated with older age (HR 2.74 per 10-year increase; 95% CI, 2.57–2.91), higher comorbidity burden (Elixhauser ≥3: HR 2.35; 95% CI, 2.05–2.68), current smoking (HR 2.21; 95% CI, 1.93–2.55), and neighborhood deprivation (ND) (highest ND Index quartile: HR 1.26; 95% CI, 1.10–1.43). Conclusions: CV death exceeded BC death by more than twofold at 10 years in Stage I, while BC was the most common cause of death in Stage III. BC mortality was influenced by more advanced stage, Black race, and Medicare insurance, whereas non-cancer mortality by older age, smoking, and higher ND and comorbidity burden. These findings support an individualized approach weighing risk of BC death against competing mortality, emphasizing comorbidity management and CV risk reduction in patients most likely to die of non-cancer causes. 5 & 10-year cumulative incidence of mortality by cause, stratified by stage. Cause of death Cancer stage 5-year CIF 10-year CIF Breast Cancer I 0.72% (0.57%, 0.91%) 2.1% (1.8%, 2.5%) II 3.4% (2.9%, 3.9%) 7.1% (6.4%, 7.9%) III 11% (9.0%, 12%) 21% (19%, 23%) Cardiovascular I 2.1% (1.8%, 2.4%) 5.5% (5.0%, 6.0%) II 2.5% (2.1%, 3.0%) 6.2% (5.5%, 6.9%) III 3.6% (2.7%, 4.6%) 7.9% (6.4%, 9.4%) OtherNon-Cancer I 1.6% (1.4%, 1.9%) 4.8% (4.3%, 5.3%) II 2.1% (1.8%, 2.6%) 5.3% (4.7%, 6.0%) III 3.0% (2.2%, 4.0%) 5.6% (4.4%, 7.0%)