title: 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.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States. mveresh@med.umich.edu.
authors.forename: Megan E V
authors.initials: MEV
authors.lastname: Caram
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States.
authors.forename: Cui
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive; Cardiovascular Center, Ann Arbor, MI, 48109, United States.
authors.forename: Monika
authors.initials: M
authors.lastname: Leja
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Smerage
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: N Lynn
authors.initials: NL
authors.lastname: Henry
authors.affiliation: Department of Pathology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: Donald
authors.initials: D
authors.lastname: Giacherio
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive; Cardiovascular Center, Ann Arbor, MI, 48109, United States.
authors.forename: Melvyn
authors.initials: M
authors.lastname: Rubenfire
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: Anne
authors.initials: A
authors.lastname: Schott
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive; Cardiovascular Center, Ann Arbor, MI, 48109, United States.
authors.forename: Melinda
authors.initials: M
authors.lastname: Davis
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Van Poznak
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.|Department of Urology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.affiliation: Department of Pharmacology, College of Pharmacy, University of Michigan , 428 Church Street, Ann Arbor, MI, 48104-1065, United States.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Hertz
authors.affiliation: Department of Biostatistics, University of Michigan School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI, 48109, United States.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Banerjee
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Medical School, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, United States.|Department of Health Management and Policy, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, 48109, United States.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Griggs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D066126:Cardiotoxicity; D004317:Doxorubicin / Q000009:adverse effects* / Q000627:therapeutic use; D004452:Echocardiography; D005260:Female; D006331:Heart Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011159:Population Surveillance; D015995:Prevalence; D012307:Risk Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D015415:Biomarkers; D004317:Doxorubicin