Cardiac Monitoring in Her-2 Positive Elderly Patients Treated with Transtuzumab

Download Article

Authors : Rajani Sinha


Human epidermal growth factor receptor -2 (HER-2) is a member of EGFR (epidermal growth factor receptor) family, plays a very significant role in cell growth and proliferation [1] HER – 2 protein is over expressed in 20% of breast cancer and is associated within aggressive course , poor prognosis and response to treatment [2-3]. The introduction of transtuzumab, a monoclonal antibody directed against, the extra cellular domain of HER -2 receptor, has revolutionized the treatment of HER – 2 positive early breast cancer and has led to significant improvement in disease free survival and overall survival over chemotherapy alone. 

In randomized multicenter trials with HER – 2 over expressing metastatic breast cancer patients, addition of transtuzumab to first line chemotherapy has improved objective response rate, the time to disease progression and overall survival over chemotherapy alone [4,5]. Hence transtummab is now considered as the standard of care for all patients who over amplify HER – 2 neu receptors.

These benefits have come with the cost of increased risk of cardiotoxicity. Transtuzumab related cardiotoxicity is mediated by interruption of normal HER – 2 signaling pathway in the heart, which is responsible for maintenance of normal growth, repair and survival of cardiomyocytes. Cardiotoxicity related to transtuzumab is different from that of anthracyclins as it is not dose related and appears to be largely reversible on discontinuation of therapy. There is no alteration is ultra structural abnormalities where as that due to anthracyclins are caused by free radical induced oxidative stress to cardiac muscles cells [12]. 


[1.] Balducci L, Exlermann M. Cancer and aging. An evolving Panorama. Hematol Oncol Clin North Am 2000; 14: 1 – 16.

[2.] Cardinale D, Colombo A, Torrisi R et al. Transtuzumab induced cardiotoxicity: Clinical and Prognostic implications of troponin I evaluation J Clin Oncol 2010; 28: 3910-3916.

[3.] Cardinale D, Sandri MT. Role of Biomarkers in Chemotherapy induced cardio toxicity Prog Cardiovasc. Dis 2010; 53: 121 – 129.

[4.] Carlson RW, Allred DC, Anderson BO et al. Breast Cancer Clinical practice guidelines in oncology J Natt Compr Cane Netw 2009; 7: 122-192.

[5.] Ewer MS,Vooletich MT,Durand JB et al. Reversibility of Transtuzumab – Related Cardiotoxicity: New Insights Based on Clinical Course and Response to Medical Treatment .J Clinoncol 2005;23:7820-7826.

[6.] Force T.Krause DS, Van Etten A. Molecular mechanisms of cardio toxicity of tyrosine kinase inhibition. Nat Rev Cancer 2007; 7; 332-344.

[7.] Fried G, Regev T ,Moskovitz M.. Transtuzumab related cardiac events in the treatment of Early breast cancer.

[8.] Goldhrisch A, Ingle JN, Gelber RD et al. Thresholds for therapies: highlights of St Gallen International Expert consensus on primary therapy of early breast cancer 2009. Ann Oncol 2009, 20: 1319-1329.

[9.] Guarneri V, Lenihan DJ, Valero V et al, Long term cardiac tolerability of transtummab in meastatic breast cancer. The M.D. Anderson Cameer Center Experience J Clin Oncol 2006; 24: 4107 – 4115

[10.]   Halyard MY, Pisanoky TM, Ducck AC et al. Radiotherapy and adjuvant transtuzumab in operable breast cancer, tolerability and adverse event data from the NCCTG phase III trail N 9831. J Clin Oncol 2009; 27: 2638 – 2644.

[11.]   Hunt SA. Acc/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to update the 2001 Guidelines for the Evaluation and Management of Heart Failure) J. Am Coll Cardiol 2005; 4b: el – e 82.

[12.]   Hutchins LF, Unger JM, Crowley J J et al. Underreparesentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999; 341: 2061-2067

[13.]   Ky B, Putt M, SawayaH, French B, Januzzi JL, Sebag IA, Plana JC, Cohen V ,Banchs J, Carver JR, Wiegers SE ,Martin RP, Picard MH, Gerszten RE, Halpern EF ,Passeri J, Kuter I, Scherrer-Crosbie M.. Early increases in multiple Biomarkers Predict Subsequent cardiotoxicity in Breast Cancer patients treated with Doxorubicin, Taxanes and transtuzumab

[14.]   L.Tarantini,S.Gori,P.Faggiano et al.Adjuvant transtuzumab cardiotoxicity in patients over 60 yrs of age with early breast cancer:a multicentric cohort study.Annals of oncology Vol 23 no 12 Dec. 2012

[15.]   Levy D, Kenchaiah S, Larson MG et al. Longterm trends in the incidence of and survival with heart failure. N Eng J med 2002; 347: 1397 – 1402.

[16.]   Marty M,Cognetti F,Maraninchi D et al.Randomised phase IItrial of efficacy and safety of transtuzumab combined with docetaxel in patients with her-2 positive metastatic breast cancer administered as first line treatment:the M77001study group.JCO 2005.

[17.]   Naumann D,Rusius V,Margiotta C,Nevill A,Carmichael A,Rea D,Sintler M. Factors predicting transtuzumab – related cardiotoxicity in a real world population of women with HER 2 + breast cancer .

[18.]   New York Heart Association Nomenclature and Criteria for Diagnosis of Disease of Heart and Great Vessels. edition Bosion, MA: Little Brown 1973.

[19.]   Palk S,Hazan R,Fisher ERet al.Pathologic findings from NSABP JCO 1990.

[20.]   Perez EA, Rodoheffer R. Clinical Cardiac tolerability of transtuzumab J clin Oncol 2004; 22; 322 – 329.

[21.]   Piotrowski G,Gawor R,Bourge RC,Stasiak A,Potemski P,Gawor Z,Nanda NC,Banach M. Heart Remodeling induced by adjuvant transtuzumab – Containing chemotherapy for breast cancer overexpressing human epidermal growth factor receptor type – 2.

[22.]   Salmon DJ, Clark GM, Wong SG et al. Human breast cancer correlation of relapse and survival with amplification of HER – 2/nen oncogene. Science 1987;235:177-182.

[23.]   Salmon DJ, Leyland-Jones B , Shak S et al .Use of chemotherapy plus a monoclonal antibody against HER-2 for metastatic breast cancer that overexpress HER-2.N Engl J med 2001;344:783-792.

[24.]   Slamon D.J, Godolphin W, Jones LA et al studies of HER – 2/men proto oncogene in human breast and ovarian cancer Science 1989.;244:707-712

[25.]   Yancik R, Wesley MN, Ries et al. Effect of age and comorbidity in post menopausal breast cancer patients aged 55 years and older JAMA 2001; 285: 885-892.