Assessment of Carvedilol Therapy in Prevention of Heart Failure in HER2 Positive Breast Cancer Patients Receiving Trastuzumab
Breast cancer is the most common cancer among the female population, and its prevalence is increasing worldwide. Trastuzumab (Herceptin) therapy improves prognosis in HER2 positive patients, but Heart Failure (HF) is one of its known complications. In this study, we aimed to assess the potential benefits of prophylactic carvedilol therapy in patients receiving Herceptin. Sixty five patients with HER2 positive breast cancer were enrolled in the study. All of the patients received Herceptin. Twenty seven patients also received carvedilol 6.25 mg twice daily, and 38 patients had usual care. Echocardiography was performed at baseline, and after three months in both groups and changes in cardiac function, parameters were compared between two groups. After 3 months, LA volume index (P=0.012), TAPSE (P=0.009), Tei index (P=0.015) and Lateral Longitudinal Strain (P=0.024) were significantly better in patients receiving carvedilol. Carvedilol can be effective in the prevention of systolic and diastolic dysfunction following Herceptin therapy.
2. Ellison, L.F. and K. Wilkins, An update on cancer survival. 2010: Statistics Canada.
3. Suter, T., N. Cook-Bruns, and C. Barton, Cardiotoxicity associated with trastuzumab (Herceptin) therapy in the treatment of metastatic breast cancer. The Breast, 2004. 13(3): p. 173-183.
4. Sparano, J.A., et al., TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score. 2018, American Society of Clinical Oncology.
5. Johansson, A.L., et al., Breast cancer survival by age and subtype (ER/PR/HER2) in a nationwide population-based cohort. 2018, AACR.
6. Baselga, J., et al., Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. The oncologist, 2006. 11(Supplement 1): p. 4-12.
7. Martin, A.P., et al., Trastuzumab uptake in HER2-positive breast cancer patients: A systematic review and meta-analysis of observational studies. Critical reviews in oncology/hematology, 2018.
8. Mohan, N., et al., Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and frontiers. Antibody therapeutics, 2018. 1(1): p. 13-17.
9. Ky, B., et al., Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. Journal of the American College of Cardiology, 2014. 63(8): p. 809-816.
10. Narayan, V. and B. Ky, Common cardiovascular complications of cancer therapy: Epidemiology, Risk Prediction, and Prevention. Annual review of medicine, 2018. 69: p. 97-111.
11. Mehrpooya, M., J. Zebardast, and M. Aghili, Breast Cancer Treatment and Cardiovascular Considerations. Archives of Breast Cancer, 2018: p. 3-10.
12. Egland, K.A., R.L. Evans, and J.V. Pottala, Reagents and Methods for Monitoring Breast Cancer Therapy. 2018, Google Patents.
13. Sandoo, A., G.D. Kitas, and A.R. Carmichael, Endothelial dysfunction as a determinant of trastuzumab-mediated cardiotoxicity in patients with breast cancer. Anticancer Research, 2014. 34(3): p. 1147-1151.
14. Cleveland, K.H., et al., Phosphoproteome profiling provides insight into the mechanism of action for carvedilol‐mediated cancer prevention. Molecular carcinogenesis, 2018.
15. Abuosa, A.M., et al., Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin. Indian heart journal, 2018.
16. Guo, D., et al., Selective inhibition on organic cation transporters by carvedilol protects mice from cisplatin-induced nephrotoxicity. Pharmaceutical research, 2018. 35(11): p. 204.
17. Huang, S., et al., Protective role of beta-blockers in chemotherapy-induced cardiotoxicity—a systematic review and meta-analysis of carvedilol. Heart failure reviews, 2018: p. 1-9.
18. Negishi, T. and K. Negishi, Echocardiographic evaluation of cardiac function after cancer chemotherapy. Journal of echocardiography, 2018. 16(1): p. 20-27.
19. Zhan, T., et al., Preventive use of carvedilol for anthracycline-induced cardiotoxicity: a systematic review and meta-analysis of randomized controlled trials. Herz, 2019: p. 1-14.
20. Schiller, N.B., et al., Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. Journal of the American Society of Echocardiography, 1989. 2(5): p. 358-367.
21. Franchi, F., et al., Assessment of left ventricular ejection fraction in critically ill patients at the time of speckle tracking echocardiography: intensivists in training for echocardiography versus experienced operators. Minerva anestesiologica, 2018.
22. Pietrzak, R. and B. Werner, Right ventricular function assessment using tissue Doppler imaging and speckle tracking echocardiography. Journal of ultrasonography, 2014. 14(58): p. 328.
23. Goroshi, M. and D. Chand, Myocardial Performance Index (Tei Index): A simple tool to identify cardiac dysfunction in patients with diabetes mellitus. Indian heart journal, 2016. 68(1): p. 83-87.
24. Nagueh, S.F., et al., Recommendations for the evaluation of left ventricular diastolic function by echocardiography. European Journal of Echocardiography, 2009. 10(2): p. 165-193.
25. Lu, D.-Y., M. Mukherjee, and T. Abraham, Principles and Practical Aspects of Strain Echocardiography. Essential Echocardiography: A Companion to Braunwald’s Heart Disease E-Book, 2017: p. 55.
26. Özben Ceylan, S.Ö., et al., Assessment of left ventricular functions with tissue Doppler, strain, and strain rate echocardiography in patients with familial Mediterranean fever. Anatolian journal of cardiology, 2016. 15(8): p. 663.
27. Seicean, S., et al., Cardioprotective effect of β-adrenoceptor blockade in patients with breast cancer undergoing chemotherapy: Follow-up study of heart failure. Circ Heart Fail. 2013; 6: 420–460. This study showed that beta-blockers were cardioprotective in breast cancer patients receiving trastuzumab and anthracycline-based chemotherapy.
28. Telli, M.L., et al., Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. Journal of Clinical Oncology, 2007. 25(23): p. 3525-3533.
29. Cardinale, D., et al., Trastuzumab-induced cardiotoxicity: clinical and prognostic implications of troponin I evaluation. Journal of Clinical Oncology, 2010. 28(25): p. 3910-3916.
30. Mehrpooya, M., et al., Trastuzumab-Induced Cardiomyopathy Evaluation by Combined Echocardiography and Biomarkers in Patients with Breast Cancer. According to the ruling of the Medical Sciences Publications Commission No. 14313-80/10/1 and 36914-85/2/10 signed by the Minister of Health and Medical Education and the Head of the Medical Sciences Publications Commission of the Islamic Republic of Iran, this journal has been granted accreditation as a scientific-research journal., 2015. 6: p. 26.
31. Kalam, K. and T.H. Marwick, Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis. European journal of cancer, 2013. 49(13): p. 2900-2909.
32. Negishi, K., et al., Use of speckle strain to assess left ventricular responses to cardiotoxic chemotherapy and cardioprotection. European Heart Journal–Cardiovascular Imaging, 2013. 15(3): p. 324-331.