Abstract
Background The use of trastuzumab is associated with an increased survival rate in HER2 positive breast cancer patients. However, it is related to different levels of cardiotoxicity leading to treatment discontinuation, which can deprive patients of the benefits of this therapy. Objective This study aimed to identify the incidence of trastuzumab induced cardiotoxicity (TIC) and the rate of discontinuation of trastuzumab in clinical practice. Possible factors associated with TIC were also investigated. Setting This study was conducted in the General Hospital of the School of Medicine of Ribeirão Preto, University of São Paulo. Methods We retrospectively reviewed the medical records of patients without distant metastasis that started trastuzumab between 2007 and 2011 in the tertiary hospital. TIC was defined as symptomatic heart failure or a decrease in left ventricular ejection fraction (LVEF) by ≥10 % compared to the first echocardiography measurement or to <50 % at any time. Logistic regression models were used to estimate odds ratios and their respective 95 % confidence intervals for TIC associated with variables such as age, body mass index, smoking history, cardiac risks, type of surgery, presence of positive lymph nodes, chemotherapy regimen and epirubicin cumulative dose. Main outcome measure The incidence and factors associated with TIC and the rate of discontinuation of trastuzumab in clinical practice. Results We analyzed the records of 79 patients. TIC developed in 26 (32.9 %) patients, being the LVEF decline by ≥10 % observed in 21 (26.6 %), a decreased to <50 % in four (5.1 %) and one (1.2 %) was symptomatic without LVEF decline. Thirteen (16.4 %) patients discontinued permanently the treatment, three (3.8 %) discontinued temporarily and 10 (12.6 %) finished it without interruption. None of the covariates influenced on the incidence of TIC in this population. Conclusion Although most patients finished their treatment, TIC led to trastuzumab discontinuation in a significant proportion of patients suggesting the need of a closer cardiac monitoring. None of the covariates influenced on the incidence of TIC, which can be due to the relatively small sample. Thus, larger scale studies should be conducted in order to establish which specific factors are associated with the development of TIC in order to avoid it.
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References
Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.
Instituto Nacional do Câncer. Estimativa 2012: Incidência de Câncer no Brasil. Rio de Janeiro: Ministério da Saúde; 2011.
Lee BL, Liedke PE, Barrios CH, et al. Breast cancer in Brazil: present status and future goals. Lancet Oncol. 2012;13:e95–102.
Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER2-2/neu oncogene. Science. 1987;235:177–82.
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344:789–92.
Murphy CG, Modi S. HER2 breast cancer therapies: a review. Biologics. 2009;3:289–301.
Yarden Y. The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer. 2001;37(Suppl 4):S3–8.
Wolff AC, Hammond ME, Schwartz JN, et al. 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. 2007;25:118–45.
Ross JS, Slodkowska EA, Symmans WF, et al. The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist. 2009;14:320–68.
Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353:1659–72.
Procter M, Suter TM, de Azambuja E, et al. Longer-term assessment of trastuzumab-related cardiac adverse events in the Herceptin Adjuvant (HERA) trial. J Clin Oncol. 2010;28:3422–8.
de Azambuja E, Bedard PL, Suter T, Piccart-Gebhart M. Cardiac toxicity with anti-HER-2 therapies: what have we learned so far? Target Oncol. 2009;4:77–88.
Guglin M, Hartlage G, Reynolds C, et al. Trastuzumab-induced cardiomyopathy: not as benign as it looks? A retrospective study. J Card Fail. 2009;15:651–7.
Wadhwa D, Fallah-Rad N, Grenier D, et al. Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: a retrospective study. Breast Cancer Res Treat. 2009;117:357–64.
Tarantini L, Cioffi G, Gori S, et al. Trastuzumab adjuvant chemotherapy and cardiotoxicity in real-world women with breast cancer. J Card Fail. 2012;18:113–19.
Farolfi A, Melegari E, Aquilina M, et al. Trastuzumab-induced cardiotoxicity in early breast cancer patients: a retrospective study of possible risk and protective factors. Heart. 2013;99:634–9.
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (HCFMRP/USP). http://www.hcrp.fmrp.usp.br/sitehc/informacao.aspx?id=5&ref=1&refV=1. Last accessed 26 May 2013.
Brasil. Portaria nº 741 de 19 de dezembro de 2005. http://portal.anvisa.gov.br/wps/wcm/connect/3092aa80474594909c3fdc3fbc4c6735/PORTARIA+N%C2%BA+741-2005.pdf?MOD=AJPERES. Last accessed 26 May 2013.
Ministério da Saúde. http://portal.saude.gov.br/portal/arquivos/pdf/Trastuzumabe_caavancado_final.pdf. Last accessed 26 May 2013.
Allison PD. Logistic regression using the SAS system: theory and application. Cary: SAS Books; 2001.
Guarneri V, Lenihan DJ, Valero V, et al. Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the MD Anderson Cancer Center experience. J Clin Oncol. 2006;24:4107–15.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 1995;353:1673–84.
Aogi K, Saeki T, Nakamura S, et al. A multicenter, phase II study of epirubicin/cyclophosphamide followed by docetaxel and concurrent trastuzumab as primary systemic therapy for HER-2 positive advanced breast cancer (the HER2NAT study). Int J Clin Oncol. 2012;. doi:10.1007/s10147-012-0437-1.
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Peto R, Davies C, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trial. Lancet. 2012;379:432–44.
Roca-Alonso L, Pellegrino L, Castellano L, et al. Breast cancer treatment and adverse cardiac events: what are the molecular mechanisms? Cardiology 2012;122:253–59.
Singal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. N Engl J Med. 1998;339:900–5.
Di Cosimo S. Heart to heart with trastuzumab: a review on cardiac toxicity. Target Oncol. 2011;6:189–95.
Ewer MS, Vooletich MT, Durand JB, et al. Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005;23:7820–6.
Chen T, Xu T, Li Y, et al. Risk of cardiac dysfunction with trastuzumab in breast cancer patients: a meta-analysis. Cancer Treat Rev. 2011;37:312–20.
Dent S, Hopkins S, Graham N. The experience of a multidisciplinary clinic in the management of early-stage breast cancer patients receiving trastuzumab therapy: an observational study. Cardiol Res Pract. 2012;2012:135819. doi:10.1155/2012/135819.
Serrano C, Cortés J, De Mattos-Arruda L, et al. Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol. 2012;23:897–902.
van Hasselt JG, Boekhout AH, Beijnen JH, et al. Population pharmacokinetic-pharmacodynamic analysis of trastuzumab-associated cardiotoxicity. Clin Pharmacol Ther. 2011;90:126–32.
Fox KF. The evaluation of left ventricular function for patients being considered for, or receiving trastuzumab (Herceptin) therapy. Br J Cancer. 2006;95:1454.
Ministério da Saúde. http://portal.saude.gov.br/portal/arquivos/pdf/Relatorio_Trastuzumabe_ca_inicial.pdf. Last accessed 26 May 2013.
Acknowledgments
The authors would like to thank the School of Pharmaceutical Sciences of Ribeirão Preto—University of São Paulo for its support during the research and the General Hospital of the Faculty of Medicine of Ribeirão Preto of the University of São Paulo (HCFMRP-USP) for its support during data collection.
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National Council for Scientific and Technological Development (CNPq).
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The authors declare that they have no conflict of interest.
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Ayres, L.R., de Almeida Campos, M.S., de Oliveira Gozzo, T. et al. Trastuzumab induced cardiotoxicity in HER2 positive breast cancer patients attended in a tertiary hospital. Int J Clin Pharm 37, 365–372 (2015). https://doi.org/10.1007/s11096-015-0070-y
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DOI: https://doi.org/10.1007/s11096-015-0070-y