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01-07-2015 | Epidemiology

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

Authors: Megan E. V. Caram, Cui Guo, Monika Leja, Jeffrey Smerage, N. Lynn Henry, Donald Giacherio, Melvyn Rubenfire, Anne Schott, Melinda Davis, Daniel F. Hayes, Catherine Van Poznak, Kathleen A. Cooney, Daniel L. Hertz, Mousumi Banerjee, Jennifer J. Griggs

Published in: Breast Cancer Research and Treatment | Issue 1/2015

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.

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Sawaya H et al (2011) Early detection and prediction of cardiotoxicity in chemotherapy-treated patients. Am J Cardiol 107(9):1375–1380CrossRefPubMedPubMedCentral

Fumoleau P et al (2006) Long-term cardiac toxicity after adjuvant epirubicin-based chemotherapy in early breast cancer: french adjuvant study group results. Ann Oncol 17(1):85–92CrossRefPubMed

Perez EA et al (2004) Effect of doxorubicin plus cyclophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 22(18):3700–3704CrossRefPubMed

Shapiro CL et al (1998) Cardiac effects of adjuvant doxorubicin and radiation therapy in breast cancer patients. J Clin Oncol 16(11):3493–3501CrossRefPubMed

Zambetti M et al (2001) Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation. J Clin Oncol 19(1):37–43CrossRefPubMed

Ganz PA et al (2008) Late cardiac effects of adjuvant chemotherapy in breast cancer survivors treated on Southwest Oncology Group protocol s8897. J Clin Oncol 26(8):1223–1230CrossRefPubMed

Doyle JJ et al (2005) Chemotherapy and cardiotoxicity in older breast cancer patients: a population-based study. J Clin Oncol 23(34):8597–8605CrossRefPubMed

Hershman DL et al (2008) Doxorubicin, cardiac risk factors, and cardiac toxicity in elderly patients with diffuse B-cell non-Hodgkin’s lymphoma. J Clin Oncol 26(19):3159–3165CrossRefPubMed

Pinder MC et al (2007) Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer. J Clin Oncol 25(25):3808–3815CrossRefPubMed

10.

Mckee PA et al (1971) Natural history of congestive heart failure—Framingham study. N Engl J Med 285(26):1441CrossRefPubMed

11.

Bart BA et al (1997) Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy. J Am Coll Cardiol 30(4):1002–1008CrossRefPubMed

12.

Trimble EL et al (1994) Representation of older patients in cancer treatment trials. Cancer 74(7 Suppl):2208–2214CrossRefPubMed

13.

Jennens RR, Giles GG, Fox RM (2006) Increasing underrepresentation of elderly patients with advanced colorectal or non-small-cell lung cancer in chemotherapy trials. Intern Med J 36(4):216–220CrossRefPubMed

14.

Hutchins LF et al (1999) Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 341(27):2061–2067CrossRefPubMed

15.

Ahmed N et al (2007) Role of cardiac troponin I in staging and prognosis of congestive heart failure subjects. Mymensingh Med J 16(1):12–16CrossRefPubMed

16.

Sundstrom J et al (2009) Cardiac troponin-I and risk of heart failure: a community-based cohort study. Eur Heart J 30(7):773–781CrossRefPubMed

17.

Vasan RS et al (2002) Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction: the Framingham heart study. JAMA 288(10):1252–1259CrossRefPubMed

18.

Redfield MM et al (2002) Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 40(5):976–982CrossRefPubMed

19.

Heidenreich PA et al (2004) Cost-effectiveness of screening with B-type natriuretic peptide to identify patients with reduced left ventricular ejection fraction. J Am Coll Cardiol 43(6):1019–1026CrossRefPubMed

20.

Poutanen T et al (2003) Long-term prospective follow-up study of cardiac function after cardiotoxic therapy for malignancy in children. J Clin Oncol 21(12):2349–2356CrossRefPubMed

21.

Palladini G et al (2003) Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 107(19):2440–2445CrossRefPubMed

22.

Wright SP et al (2003) Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care: a randomized, controlled trial. J Am Coll Cardiol 42(10):1793–1800CrossRefPubMed

23.

Ng LL et al (2005) Community screening for left ventricular systolic dysfunction using plasma and urinary natriuretic peptides. J Am Coll Cardiol 45(7):1043–1050CrossRefPubMed

24.

Hildebrandt P et al (2010) Age-dependent values of N-terminal pro-B-type natriuretic peptide are superior to a single cut-point for ruling out suspected systolic dysfunction in primary care. Eur Heart J 31(15):1881–1889CrossRefPubMed

25.

Betti I et al (2009) The role of N-terminal PRO-brain natriuretic peptide and echocardiography for screening asymptomatic left ventricular dysfunction in a population at high risk for heart failure. The PROBE-HF study. J Card Fail 15(5):377–384CrossRefPubMed

26.

Maisel AS et al (2001) Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction. Am Heart J 141(3):367–374CrossRefPubMed

27.

Lang RM et al (2005) Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 18(12):1440–1463CrossRefPubMed

28.

Ammar KA et al (2007) Prevalence and prognostic significance of heart failure stages: application of the American College of Cardiology/American Heart Association heart failure staging criteria in the community. Circulation 115(12):1563–1570CrossRefPubMed

29.

Redfield MM et al (2003) Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 289(2):194–202CrossRefPubMed

30.

Perez EA, Rodeheffer R (2004) Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22(2):322–329CrossRefPubMed

31.

Tan-Chiu E et al (2005) Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol 23(31):7811–7819CrossRefPubMed

32.

Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer 97(11):2869–2879CrossRefPubMed

33.

Solvd Investigators (1992) Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 327(10):685–691CrossRef

34.

Yancy CW et al (2013) 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128(16):1810–1852CrossRefPubMed

35.

Cardinale D et al (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114(23):2474–2481CrossRefPubMed

36.

Kalay N et al (2006) Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 48(11):2258–2262CrossRefPubMed

37.

Jones SE et al (2006) Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24(34):5381–5387CrossRefPubMed

38.

Giordano SH et al (2012) Decline in the use of anthracyclines for breast cancer. J Clin Oncol 30(18):2232–2239CrossRefPubMedPubMedCentral

Title: Doxorubicin-induced cardiac dysfunction in unselected patients with a history of early-stage breast cancer
Authors: Megan E. V. Caram
Cui Guo
Monika Leja
Jeffrey Smerage
N. Lynn Henry
Donald Giacherio
Melvyn Rubenfire
Anne Schott
Melinda Davis
Daniel F. Hayes
Catherine Van Poznak
Kathleen A. Cooney
Daniel L. Hertz
Mousumi Banerjee
Jennifer J. Griggs
Publication date: 01-07-2015
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-015-3454-8

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