Doxorubicin-induced cardiac dysfunction in unselected patients with a history of early-stage breast cancer

Abstract

Cardiomyopathy is a known complication of anthracycline-based adjuvant chemotherapy and is more commonly reported in population-based studies of breast cancer survivors than in clinical trials. This study prospectively evaluated the prevalence of elevated cardiac biomarkers in unselected patients who had been treated with doxorubicin for early-stage breast cancer and the prevalence of reduced LVEF in patients with an elevated biomarker. All participants underwent an examination, symptom inventory, medical record review, and biomarker analysis for BNP, troponin, and plasma and urine NT-proBNP. Patients who had one or more elevated biomarkers were referred for echocardiogram; systolic dysfunction was defined as LVEF less than 55 %. Multivariable logistic regression was used to determine the associations between age, BMI, cumulative dose of doxorubicin, diabetes, hypertension, and left-sided radiation therapy and the risk of reduced LVEF. Among the 269 patients who underwent lab testing (mean age 56 years, mean time since completion of doxorubicin-based chemotherapy 6 years), 192 (72 %) had one or more elevated biomarker. Among the 166 patients who completed an echocardiogram, 11.5 % had a LVEF < 55 %. After adjusting for covariates known to affect cardiac function, multivariable logistic regression revealed plasma NT-proBNP to be the only measured cardiac biomarker associated with systolic dysfunction. There is a relationship between NT-proBNP and the frequency of reduced LVEF in women treated with doxorubicin for curative intent; further study of NT-proBNP as a potential biomarker for subclinical cardiac dysfunction after exposure to anthracyclines is warranted.

Evidence for Association of SNPs in ABCB1 and CBR3 , but not RAC2, NCF4, SLC28A3 or TOP2B , with Chronic Cardiotoxicity in a Cohort of Breast Cancer Patients Treated with Anthracyclines

“…Among the 293 subjects enrolled into the parent clinical study [14], 166 underwent echocardiogram due to known anthracycline-induced CHF or an abnormal biomarker suggestive of CHF. Of these 166 echocardiograms, 19 cases of systolic dysfunction (EF <55%) were identified for comparison with the control group of 147 patients who had a normal echocardiogram (Figure 1).…”

“…Detailed information regarding the parent clinical study cohort, procedures and findings can be found in the primary publication [14]. Briefly, patients seen in the Breast Oncology Program who had completed neoadjuvant or adjuvant chemotherapy with a doxorubicin-based regimen for stage I-III breast cancer and received their last dose of doxorubicin at least 12 months prior were eligible for enrollment.…”

Myocardial dysfunction in long‐term breast cancer survivors treated at ages 40–50 years

“…Caram et al 25 did evaluate the prevalence of cardiac dysfunction by a biomarker assay and an echocardiogram. They found that LVEF <55% was present in 11.5% of doxorubicin-treated BC survivors (median age: 56 years, median follow-up: 6 years) with an elevated cardiac biomarker at first screening (71% of included patients).…”

Late effecten van borstkankerbehandeling op het hart

“…vonden. 12,19 Het percentage met een LVEF < 50% in ons onderzoek (4,1%) kwam wel overeen met eerdere onderzoeken, die bij een follow-upduur van vijf tot veertien jaar uitkwamen op 1,4 tot 8%. 10,12,20,21 De verschillen tussen de uitkomsten worden verklaard door verschillen in inclusiecriteria (tijd vanaf diagnose, chemotherapieregime, leeftijd).…”