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Anthony A. Matthews, Sharon Peacock Hinton, Susannah Stanway, Alexander R. Lyon, Liam Smeeth, Krishnan Bhaskaran and Jennifer L. Lund

Background: It has been suggested that cardiovascular risks are increased in breast cancer survivors, but few studies have quantified the risks of a range of specific clinically important cardiovascular outcomes in detail. Patients and Methods: Women aged >65 years with incident breast cancer from 2004 to 2013 in the SEER-Medicare linked database were matched with 5 cancer-free female counterparts (5:1 ratio). Prevalence of specific cardiovascular outcomes at baseline was measured, then Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals for the risk of individual cardiovascular outcomes during follow-up. Modification of the effect was investigated by time since diagnosis, race/ethnicity, prior cardiovascular disease (CVD), and age. Results: In all, 91,473 women with breast cancer and 454,197 without breast cancer were included. Women with breast cancer had lower baseline prevalence of all CVDs. Compared with cancer-free controls, breast cancer survivors had substantially increased risks of deep vein thrombosis (adjusted HR, 1.67; 95% CI, 1.62–1.73; 386,484 person-years of follow-up) and pericarditis (HR, 1.43; 95% CI, 1.38–1.49; 390,776 person-years of follow-up); evidence of smaller increased risks of sudden cardiac arrest, arrhythmia, heart failure, and valvular heart disease (adjusted HRs ranging from 1.05–1.09, lower CI limits all ≥1); and evidence of lower risk of incident angina, myocardial infarction, revascularization, peripheral vascular disease, and stroke (adjusted HRs ranging from 0.89–0.98, upper CI limits all ≤1). Increased risks of arrhythmia, heart failure, pericarditis, and deep vein thrombosis persisted >5 years after cancer diagnosis. Conclusions: Women with a history of breast cancer were at increased risk of several CVDs, persisting into survivorship. Monitoring and managing cardiovascular risk throughout the long-term follow-up of women diagnosed with breast cancer should be a priority.

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Emily J. Guerard, Allison M. Deal, YunKyung Chang, Grant R. Williams, Kirsten A. Nyrop, Mackenzi Pergolotti, Hyman B. Muss, Hanna K. Sanoff and Jennifer L. Lund

Background: An objective measure is needed to identify frail older adults with cancer who are at increased risk for poor health outcomes. The primary objective of this study was to develop a frailty index from a cancer-specific geriatric assessment (GA) and evaluate its ability to predict all-cause mortality among older adults with cancer. Patients and Methods: Using a unique and novel data set that brings together GA data with cancer-specific and long-term mortality data, we developed the Carolina Frailty Index (CFI) from a cancer-specific GA based on the principles of deficit accumulation. CFI scores (range, 0–1) were categorized as robust (0–0.2), pre-frail (0.2–0.35), and frail (>0.35). The primary outcome for evaluating predictive validity was all-cause mortality. The Kaplan-Meier method and log-rank tests were used to compare survival between frailty groups, and Cox proportional hazards regression models were used to evaluate associations. Results: In our sample of 546 older adults with cancer, the median age was 72 years, 72% were women, 85% were white, and 47% had a breast cancer diagnosis. Overall, 58% of patients were robust, 24% were pre-frail, and 18% were frail. The estimated 5-year survival rate was 72% in robust patients, 58% in pre-frail patients, and 34% in frail patients (log-rank test, P<.0001). Frail patients had more than a 2-fold increased risk of all-cause mortality compared with robust patients (adjusted hazard ratio, 2.36; 95% CI, 1.51–3.68). Conclusions: The CFI was predictive of all-cause mortality in older adults with cancer, a finding that was independent of age, sex, cancer type and stage, and number of medical comorbidities. The CFI has the potential to become a tool that oncologists can use to objectively identify frailty in older adults with cancer.