Valvular heart disease as a possible predictor of trastuzumab‑induced cardiotoxicity in patients with breast cancer

Sato,Akihiko; Yoshihisa,Akiomi; Miyata‑Tatsumi,Makiko; Oikawa,Masayoshi; Kobayashi,Atsushi; Ishida,Takafumi; Ohtake,Tohru; Takeishi,Yasuchika

doi:10.3892/mco.2018.1764

Valvular heart disease as a possible predictor of trastuzumab‑induced cardiotoxicity in patients with breast cancer

Authors:
- Akihiko Sato
- Akiomi Yoshihisa
- Makiko Miyata‑Tatsumi
- Masayoshi Oikawa
- Atsushi Kobayashi
- Takafumi Ishida
- Tohru Ohtake
- Yasuchika Takeishi
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Affiliations: Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Fukushima 960‑1295, Japan, Department of Breast Surgery, Fukushima Medical University, Fukushima, Fukushima 960‑1295, Japan
Published online on: November 13, 2018 https://doi.org/10.3892/mco.2018.1764
Pages: 37-42
Copyright: © Sato et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although the use of trastuzumab has been reported to improve overall survival in patients with HER2‑positive breast cancer, there is increasing concern about the adverse effects of trastuzumab‑induced cardiotoxicity (TIC). The aim of the present study was to investigate the predictor of TIC and to consider appropriate management for such patients. The present study breast cancer 119 patients with breast cancer who had been treated with trastuzumab. Patients were referred to our department for cardiac function screening. The patients' baseline characteristics, echocardiographic data, presence of trastuzumab‑induced cardiotoxicity (TIC) and all‑cause mortality were investigated. TIC was defined as a manifestation of overt heart failure or ≥10% reduction of left ventricular ejection fraction (LVEF) from baseline to an LVEF <55% in asymptomatic patients. During the follow‑up period (mean, 1,410 days), symptomatic heart failure occurred in 2 out of 119 patients (1.6%), 11 patients (9.2%) had asymptomatic impairment of cardiac function that was ameliorated by discontinuing trastuzumab and 20 patients (16.8%) succumbed to cancer‑associated fatality. In the logistic regression analysis, only the presence of valvular heart disease at the baseline was indicated to be a predictor of TIC. There was no other predictor for TIC, including baseline characteristics, other therapies and echocardiographic parameters. In addition, impairment of cardiac function was ameliorated by discontinuing trastuzumab. TIC occurred in ~10% of the patients treated with trastuzumab. Only the presence of valvular heart disease seems to be associated with occurrence of TIC, with no other specific predictor of TIC demonstrated in the present study. The present data suggests the importance of regular monitoring of cardiac function, and that presence of valvular heart disease may be a possible predictor of TIC.

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1	Miller KD, Siegel RL, Lin CC, Mariotto AB, Kramer JL, Rowland JH, Stein KD, Alteri R and Jemal A: Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin. 66:271–289. 2016. View Article : Google Scholar : PubMed/NCBI
2	Santhosh S, Kumar P, Ramprasad V and Chaudhuri A: Evolution of targeted therapies in cancer: Opportunities and challenges in the clinic. Future Oncol. 11:279–293. 2015. View Article : Google Scholar : PubMed/NCBI
3	Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, Habib G, Lenihan DJ, Lip GYH, Lyon AR, et al: Group ESCSD. 2016 esc position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the esc committee for practice guidelines: The task force for cancer treatments and cardiovascular toxicity of the european society of cardiology (esc). Eur Heart J. 37:2768–2801. 2016. View Article : Google Scholar : PubMed/NCBI
4	Lal H, Kolaja KL and Force T: Cancer genetics and the cardiotoxicity of the therapeutics. J Am Coll Cardiol. 61:267–274. 2013. View Article : Google Scholar : PubMed/NCBI
5	Nikolai BC, Lanz RB, York B, Dasgupta S, Mitsiades N, Creighton CJ, Tsimelzon A, Hilsenbeck SG, Lonard DM, Smith CL and O'Malley BW: HER2 signaling drives DNA anabolism and proliferation through SRC-3 phosphorylation and E2F1-regulated genes. Cancer Res. 76:1463–1475. 2016. View Article : Google Scholar : PubMed/NCBI
6	Hudis CA: Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med. 357:39–51. 2007. View Article : Google Scholar : PubMed/NCBI
7	Pritchard KI, Shepherd LE, O'Malley FP, Andrulis IL, Tu D, Bramwell VH and Levine MN: National Cancer Institute of Canada Clinical Trials Group: HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med. 354:2103–2111. 2006. View Article : Google Scholar : PubMed/NCBI
8	Perez EA, Romond EH, Suman VJ, Jeong JH, Sledge G, Geyer CE Jr, Martino S, Rastogi P, Gralow J, Swain SM, et al: Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: Planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 32:3744–3752. 2014. View Article : Google Scholar : PubMed/NCBI
9	Criscitiello C and Curigliano G: HER2 signaling pathway and trastuzumab cardiotoxicity. Future Oncol. 9:179–181. 2013. View Article : Google Scholar : PubMed/NCBI
10	Negro A, Brar BK and Lee KF: Essential roles of Her2/erbB2 in cardiac development and function. Recent Prog Horm Res. 59:1–12. 2004. View Article : Google Scholar : PubMed/NCBI
11	Bloom MW, Hamo CE, Cardinale D, Ky B, Nohria A, Baer L, Skopicki H, Lenihan DJ, Gheorghiade M, Lyon AR and Butler J: Cancer therapy-related cardiac dysfunction and heart failure: Part 1: Definitions, pathophysiology, risk factors and imaging. Circ Heart Fail. 9:e0026612016. View Article : Google Scholar : PubMed/NCBI
12	Ezaz G, Long JB, Gross CP and Chen J: Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Heart Assoc. 3:e0004722014. View Article : Google Scholar : PubMed/NCBI
13	Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, de Azambuja E, Procter M, Suter TM, Jackisch C, Cameron D, Weber HA, Heinzmann D, et al: 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): An open-label, randomised controlled trial. Lancet. 382:1021–1028. 2013. View Article : Google Scholar : PubMed/NCBI
14	McKee PA, Castelli WP, McNamara PM and Kannel WB: The natural history of congestive heart failure: The framingham study. N Engl J Med. 285:1441–1446. 1971. View Article : Google Scholar : PubMed/NCBI
15	Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ and Keefe D: Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 20:1215–1221. 2002. View Article : Google Scholar : PubMed/NCBI
16	Brown SA, Sandhu N and Herrmann J: Systems biology approaches to adverse drug effects: The example of cardio-oncology. Nat Rev Clin Oncol. 12:718–731. 2015. View Article : Google Scholar : PubMed/NCBI
17	Guglin M, Cutro R and Mishkin JD: Trastuzumab-induced cardiomyopathy. J Card Fail. 14:437–444. 2008. View Article : Google Scholar : PubMed/NCBI
18	Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, Allen LA, Nekhlyudov L, Goddard KA, Davis RL, et al: Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: A retrospective cohort study. J Natl Cancer Inst. 104:1293–1305. 2012. View Article : Google Scholar : PubMed/NCBI
19	Smith LA, Cornelius VR, Plummer CJ, Levitt G, Verrill M, Canney P and Jones A: Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 10:3372010. View Article : Google Scholar : PubMed/NCBI
20	Russell SD, Blackwell KL, Lawrence J, Pippen JE Jr, Roe MT, Wood F, Paton V, Holmgren E and Mahaffey KW: Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: A combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials. J Clin Oncol. 28:3416–3421. 2010. View Article : Google Scholar : PubMed/NCBI
21	Yu AF, Yadav NU, Eaton AA, Lung BY, Thaler HT, Liu JE, Hudis CA, Dang CT and Steingart RM: Continuous trastuzumab therapy in breast cancer patients with asymptomatic left ventricular dysfunction. Oncologist. 20:1105–1110. 2015. View Article : Google Scholar : PubMed/NCBI
22	Martin M, Esteva FJ, Alba E, Khandheria B, Pérez-Isla L, García-Sáenz JA, Márquez A, Sengupta P and Zamorano J: Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: Review and expert recommendations. Oncologist. 14:1–11. 2009. View Article : Google Scholar : PubMed/NCBI
23	Hensley ML, Schuchter LM, Lindley C, Meropol NJ, Cohen GI, Broder G, Gradishar WJ, Green DM, Langdon RJ Jr, Mitchell RB, et al: American society of clinical oncology clinical practice guidelines for the use of chemotherapy and radiotherapy protectants. J Clin Oncol. 17:3333–3355. 1999. View Article : Google Scholar : PubMed/NCBI
24	Hering D, Faber L and Horstkotte D: Echocardiographic features of radiation-associated valvular disease. Am J Cardiol. 92:226–230. 2003. View Article : Google Scholar : PubMed/NCBI
25	Tassan-Mangina S, Codorean D, Metivier M, Costa B, Himberlin C, Jouannaud C, Blaise AM, Elaerts J and Nazeyrollas P: Tissue doppler imaging and conventional echocardiography after anthracycline treatment in adults: Early and late alterations of left ventricular function during a prospective study. Eur J Echocardiogr. 7:141–146. 2006. View Article : Google Scholar : PubMed/NCBI
26	Oreto L, Todaro MC, Umland MM, Kramer C, Qamar R, Carerj S, Khandheria BK and Paterick TE: Use of echocardiography to evaluate the cardiac effects of therapies used in cancer treatment: What do we know? J Am Soc Echocardiogr. 25:1141–1152. 2012. View Article : Google Scholar : PubMed/NCBI
27	Ferté C, Massard C, Cohen A, Soria JC and Ederhy S: Trastuzumab-induced cardiotoxicity: Is it time for troponin for all patients? Am J Clin Oncol. 35:183–184. 2012. View Article : Google Scholar : PubMed/NCBI
28	Cardinale D, Colombo A, Torrisi R, Sandri MT, Civelli M, Salvatici M, Lamantia G, Colombo N, Cortinovis S, Dessanai MA, et al: Trastuzumab-induced cardiotoxicity: Clinical and prognostic implications of troponin i evaluation. J Clin Oncol. 28:3910–3916. 2010. View Article : Google Scholar : PubMed/NCBI