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Background Breast cancer therapies are associated with a risk of cardiac dysfunction, most commonly defined by changes in left ventricular ejection fraction (LVEF). Recently, the authors identified 3 classes of LVEF change after exposure to anthracyclines and/or trastuzumab using latent class growth modeling. The objective of the current study was to characterize the clinical, biochemical, and functional profiles associated with LVEF trajectory class membership. Methods Transthoracic echocardiography and biomarker assessments were performed and questionnaires were administered at standardized intervals in a longitudinal cohort of 314 patients with breast cancer who were treated with anthracyclines and/or trastuzumab. Univariable and multivariable multinomial regression analyses evaluated associations between baseline variables and LVEF trajectory class membership. Generalized estimating equations were used to define mean changes in cardiovascular measures over time within each class. Results Among the 3 distinct subgroups of LVEF changes identified (stable [class 1]; modest, persistent decline [class 2]; and significant early decline followed by partial recovery [class 3]), higher baseline LVEF, radiotherapy, and sequential therapy with anthracyclines and/or trastuzumab were associated with class 2 or 3 membership. Sustained abnormalities in longitudinal strain and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were observed in patients in class 2, as were heart failure symptoms. Similar abnormalities were observed in patients in class 3, but there was a trend toward recovery, particularly for longitudinal strain. Conclusions Patients with modest, persistent LVEF declines experienced sustained abnormalities in imaging and biochemical markers of cardiac function and heart failure symptoms. Further investigation is needed to characterize the long-term risk of heart failure, particularly in those with modest LVEF declines.

Breast cancer is commonly diagnosed in postmenopausal women, the majority of whom express 1 or more cardiovascular disease risk factors. Cardiovascular disease poses a significant competing risk for morbidity and mortality among nonmetastatic breast cancer survivors. Adjuvant systemic therapies may result in late-cardiac toxicity decades after treatment completion. The cumulative incidence of treatment-related cardiotoxic outcomes may be as high as 33% after some adjuvant breast cancer therapies. Breast cancer treatment-induced cardiotoxicity may manifest as cardiomyopathy, coronary ischemia, thromboembolism, arrhythmias and conduction abnormalities, and valvular and pericardial disease. Evidence indicates that preexisting cardiovascular conditions such as hypertension or left ventricular dysfunction may compound the adverse effects of cardiotoxic treatments. There are currently no published clinical practice guidelines that address ongoing cardiac surveillance for cardiotoxicity after breast cancer, and existing guidelines for monitoring and promoting cardiovascular health in older women are often not followed. The multidisciplinary prospective surveillance system proposed elsewhere in this supplement would allow for earlier detection of cardiotoxicity from treatment and may improve monitoring of cardiovascular health in the growing population of breast cancer survivors.

BACKGROUND Long-term survivors of testicular cancer (TC) who received cisplatin-based chemotherapy have an increased risk of cardiovascular disease. A cross-sectional study was performed to objectively assess cardiovascular risk, subclinical atherosclerosis, and endothelial function in long-term survivors of TC. METHODS Long-term survivors of TC underwent evaluation including determination of body mass index (BMI), Framingham relative risk (RR), brachial artery flow-mediated dilatation (FMD), carotid artery intima-media thickness (IMT), soluble intercellular adhesion molecule-1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and flow cytometric analysis of peripheral blood for levels of endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs). TC survivors who received chemotherapy were compared with a chemotherapy naive cohort. RESULTS Twenty-four patients received cisplatin-based chemotherapy (CBCT) and 15 were chemotherapy-naive (CN). The CBCT cohort demonstrated more impairment of brachial artery FMD than the CN group (5.6% vs 8.8%; P = .05). The mean sICAM was also found to be higher in the CBCT cohort compared with the CN group (P = .04). No significant differences between the groups were noted with regard to BMI, Framingham RR, carotid IMT, or hs-CRP. In a subset of patients, TC survivors who received chemotherapy had a significantly increased level of CECs compared with CN patients (P = .04). No significant difference in EPC levels was detected. CONCLUSIONS Long-term survivors of TC who received chemotherapy demonstrate objective evidence of endothelial injury and dysfunction, a potential mechanism for increased cardiovascular risk. Cancer 2008. © 2008 American Cancer Society.