Abstract
Trastuzumab is considered a cornerstone in the treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Cardiac toxicity is an important side effect of treatment and can limit the use of this drug known to act synergistically with cardiotoxicity from anthracyclines. A retrospective study was performed on breast cancer patients with early breast cancer, and HER2 overexpression treated with adjuvant/neoadjuvant chemotherapy and trastuzumab between 2005 and 2010. Cardiac events (CE) were recorded if left ventricular ejection fraction (LVEF) reduction was more than 10 % from baseline echocardiography. Treatment-related potential risk and protective factors were recorded. Median age of the 124 patients included in this analysis was 51 years (range 29–70 years). Treatment regimens were anthracycline-cyclophosphamide (AC)-Taxol (105 patients), TCH (12 patients), and CAF/Taxol combination (7 patients). CE were observed in 26 (21 %) patients. Trastuzumab was stopped in 9 (7 %) patients and rechallenged in five after periods ranging from 19 to 120 days. There was a significant decrease in LVEF between baseline/post-AC and during trastuzumab treatment (mean LVEF 64.29 vs. 61.97 %, p < 0.001). Treatment-related risk factors were age and interval since last AC. Trastuzumab loading dose (8 vs. 4 mg) did not influence CE rate. 56 (45 %) patients received left chest wall irradiation with significantly increased CE rates, 16 (31.4 %) versus 10 (15.4 %), in patients without radiotherapy (p < 0.05). The presence of any cardiac risk factor caused a trend toward increased risk, not statistically significant. No connection was found between possible cardioprotective drugs and reduced rates of toxicity. The incidence of cardiac toxicity with trastuzumab adjuvant treatment in our study is similar to other reports. Only radiotherapy to the left chest wall increased the risk for CE. Further prospective studies are needed, including echocardiographic measurement and biochemical data (troponin I), for early recognition and monitoring of high-risk patients.
Similar content being viewed by others
References
American Cancer Society (2012) American Cancer Society Statistics 2012. http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-032009.pdf. Accessed 20 Nov 2012
“Annual Reports: Breast Cancer (Invasive).” Israel Ministry of Health.www.old.health.gov.il/pages/default.asp?maincat=22&catid=183&pageid=1609
Lamerato L, Havstad S, Gandhi S, Jones D, Chlebowski R (2005) Breast cancer recurrence and related mortality in U.S. pts with early breast cancer. J Clin Oncol 2005 ASCO Annual Meeting Proceedings 23:738
Zeglinski M, Ludke A, Jassal DS, Singal PK (2011) Trastuzumab-induced cardiac dysfunction: A ‘dual-hit’. Exp Clin Cardiol 16:70–74
Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, ESMO Guidelines Working Group et al (2012) Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Ann Oncol 23(Suppl 7):vii155–166
Azambuja ED, Bedard PL, Suter T, Piccart-Gebhart M (2009) Cardiac toxicity with anti-HER-2 therapies - what have we learned so far? Target Oncol 2:77–88
Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M et al (2010) Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. J Clin Oncol 28:3910–3916
Perez EA, Suman VJ, Davidson NE, Sledge GW, Kaufman PA et al (2008) Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial. J Clin Oncol 26:1231–1238
Halyard MY, Pisansky TM, Dueck AC, Suman V, Pierce L et al (2009) Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. J Clin Oncol 27:2638–2644
Piotrowski G, Gawor R, Stasiak A, Gawor Z, Potemski P, Banach M (2012) Cardiac complications associated with trastuzumab in the setting of adjuvant chemotherapy for breast cancer overexpressing human epidermal growth factor receptor type 2—a prospective study. Arch Med Sci 8:227–235
Perez E, Suman V, Davidson N, Kaufman P, Martino S et al (2004) Effect of doxorubicin plus cccylophosphamide on left ventricular ejection fraction in patients with breast cancer in the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. J Clin Oncol 22:3700–3704
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A (2010) AJCC cancer staging manual, 7th edn. Springer, New York
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred CD et al (2007) American Society of Clinical Oncology/College of American Pathologists Guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145
Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A et al (2007) 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 369:29–36
Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M et al (2011) Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 365:1263–1273
Bird BR, Swain SM (2008) Cardiotoxicity in breast cancer survivors: review of potential cardiac problems. Clin Cancer Res 14:14–24
Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M 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 23:7811–7819
Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V et al (2005) Trastuzumab in combination with docetaxel or vinorelbine as adjuvant treatment of breast cancer: the FinHer Trial. Breast Cancer Res Treat 94(Suppl 1):5S
Fiuza M, Magalhães A. Trastuzumab and cardiotoxicity, cardiotoxicity of oncologic treatments, Manuela Fiuza (Ed.), ISBN: 978-953-51-0273-1, InTech, doi:10.5772/34093. Available from: http://www.intechopen.com/books/cardiotoxicity-of-oncologic-treatments/trastuzumab-and-cardiotoxicity
Guglin M, Hartlage G, Reynolds C, Chen R, Patel V (2009) Trastuzumab-induced cardiomyopathy: not as benign as it looks? a retrospective study. J Card Fail 15:651–657
Tarantini L, Cioffi G, Gori S, Tuccia F, Boccardi L et al (2012) Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail 18:113–119
Wadhwa D, Fallah-Rad N, Grenier D, Krahn M, Fang T et al (2009) Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study. Breast Cancer Res Treat 117:357–364
Cardinale D, Sandri MT, Martinoni A, Borghini E, Civelli M et al (2002) Myocardial injury revealed by plasma troponin I in breast cancer treated with high-dose chemotherapy. Ann Oncol 13:710–715
Cardinale D, Sandri MT, Colombo A, Colombo N, Boeri M et al (2004) Prognostic value of troponin I in cardiac risk stratification of cancer patients undergoing high-dose chemotherapy. Circulation 109:2749–2754
Pichon MF, Cvitkovic F, Hacene K, Delaunay J, Lokiec F et al (2005) Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide assays and radionuclide ventriculography. In Vivo 19:567–576
Serrano C, Cortés J, De Mattos-Arruda L, Bellet M, Gómez P et al (2012) Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 23:897–902
Cardinale D, Colombo A, Sandri MT, Lamantia G, Colombo N et al (2006) Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation 114:2474–2481
Kalay N, Basar E, Ozdogru I, Er O, Cetinkaya Y et al (2006) Protective effects of carvedilol against anthracycline-induced cardiomyopathy. J Am Coll Cardiol 48:2258–2262
Author information
Authors and Affiliations
Corresponding author
Additional information
G. Fried and T. Regev are contributed equally to this article.
Rights and permissions
About this article
Cite this article
Fried, G., Regev, T. & Moskovitz, M. Trastuzumab-related cardiac events in the treatment of early breast cancer. Breast Cancer Res Treat 142, 1–7 (2013). https://doi.org/10.1007/s10549-013-2732-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-013-2732-6