Factors associated with the recovery of chemotherapy induced cardiomyopathy in HER2 overexpressing breast cancer

Main Article Content

Eser Açıkgöz
Sadık Kadri Açıkgöz
Ülkü Yalçıntaş Arslan
İmran Ceren

Abstract

Objective: Chemotherapy induced cardiomyopathy (CI-CMP) is an important and potentially deadly complication of chemotherapy. However, factors associated with the recovery of CI-CMP have not been studied adequately so far. In this study, determinants of the recovery of CI-CMP in HER2 overexpressing breast cancer patients who received a chemotherapy regimen consisting of Doxorubicin, Trastuzumab, Paclitaxel and Cyclophosphamide and developed CI-CMP were investigated.


Material and Methods: 88 patients with CI-CMP among 1.410 HER2 positive breast cancer patients were enrolled and followed up for a median of 64 months. A multivariate logistic regression analysis model was used to assess the association between recovery of CI-CMP and other variables


Results: The median age of the participants was 52, and similar between groups. CI-CMP was recovered in 52 patients (59.1 %). Hypertension, diabetes mellitus, clinical heart failure, ECG anomaly, visceral metastasis, heart rate and blood glucose were significantly lower in recovered patients. A multivariate logistic regression analysis revealed that diabetes mellitus (OR 0.030, CI 0.010-0.083, p<0.001), heart rate (OR 0.799, CI 0.700-0.913, p<0.001), minimum LVEF during follow-up (OR 1.115, CI 1.015-1.223, p=0.03), development of clinical heart failure (OR 0.238, CI 0.098-0.876, p=0.022) and visceral metastasis (OR 0.022, CI 0.002-0.226, p=0.001) were independent predictors of the recovery of CI-CMP.


Conclusion: According to our results, Diabetes mellitus, heart rate, minimum LVEF during follow-up, development of clinical heart failure, and presence of visceral metastasis were independently associated with the recovery of CI-CMP. Particularly, relationship between diabetes and recovery of CI-CMP is notable and deserves further research.

Downloads

Download data is not yet available.

Article Details

How to Cite
Açıkgöz, E., Açıkgöz, S. K. ., Arslan , Ülkü Y. ., & Ceren , İmran . (2022). Factors associated with the recovery of chemotherapy induced cardiomyopathy in HER2 overexpressing breast cancer. Medical Science and Discovery, 9(5), 283–287. https://doi.org/10.36472/msd.v9i5.736
Section
Research Article
Received 2022-04-26
Accepted 2022-05-09
Published 2022-05-17

References

Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29. doi: 10.3322/caac.21208. Epub 2014 Jan 7. Erratum in: CA Cancer J Clin. 2014 Sep-Oct;64(5):364. DOI: https://doi.org/10.3322/caac.21208

Curigliano G, Cardinale D, Dent S, Criscitiello C, Aseyev O, Lenihan D, Cipolla CM. Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA Cancer J Clin. 2016 Jul;66(4):309-25. doi: 10.3322/caac.21341. Epub 2016 Feb 26. DOI: https://doi.org/10.3322/caac.21341

Smith L.A., Cornelius V.R., Plummer C.J., Levitt G., Verrill M., Canney P., Jones A. Cardiotoxicity of anthracycline agents for the treatment of cancer: Systematic review and meta-analysis of randomised controlled trials. BMC Cancer. 2010;10:337 DOI: https://doi.org/10.1186/1471-2407-10-337

Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, Bauerfeind I, Hilfrich J, Eidtmann H, Gerber B, Hanusch C, Kühn T, du Bois A, Blohmer JU, Thomssen C, Dan Costa S, Jackisch C, Kaufmann M, Mehta K, von Minckwitz G. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010 Apr 20;28(12):2024-31. doi: 10.1200/JCO.2009.23.8451. DOI: https://doi.org/10.1200/JCO.2009.23.8451

Anthracycline- and trastuzumab-induced cardiotoxicity: a retrospective study.Hamirani Y, Fanous I, Kramer CM, Wong A, Salerno M, Dillon P Med Oncol. 2016 Jul; 33(7):82. DOI: https://doi.org/10.1007/s12032-016-0797-x

Ezaz G, Long JB, Gross CP, Chen J. Risk prediction model for heart failure and cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Heart Assoc. 2014 Feb 28;3(1):e000472. doi: 10.1161/JAHA.113.000472. DOI: https://doi.org/10.1161/JAHA.113.000472

Varricchi G, Ameri P, Cadeddu C, Ghigo A, Madonna R, Marone G, et al. Antineoplastic drug-induced cardiotoxicity: a redox perspective. Front Physiol. 2018;9:167. https://doi.org/10.3389/fphys.2018.00167. DOI: https://doi.org/10.3389/fphys.2018.00167

Vejpongsa P, Yeh ET. Prevention of anthracyclineinduced cardiotoxicity: challenges and opportunities. J Am Coll Cardiol. 2014;64(9):938–45. https://doi.org/10.1016/j.jacc.2014.06.1167. DOI: https://doi.org/10.1016/j.jacc.2014.06.1167

Mohan N, Shen Y, Endo Y, ElZarrad MK, Wu WJ. Trastuzumab, but Not Pertuzumab, Dysregulates HER2 Signaling to Mediate Inhibition of Autophagy and Increase in Reactive Oxygen Species Production in Human Cardiomyocytes. Mol Cancer Ther. 2016 Jun;15(6):1321-31. doi: 10.1158/1535-7163.MCT-15-0741. Epub 2016 Mar 29. PMID: 27197303. DOI: https://doi.org/10.1158/1535-7163.MCT-15-0741

Mohan N, Jiang J, Dokmanovic M, Wu WJ. Trastuzumab-mediated cardiotoxicity: current understanding, challenges, and frontiers. Antib Ther. 2018 Aug 31;1(1):13-17. doi: 10.1093/abt/tby003. DOI: https://doi.org/10.1093/abt/tby003

Braverman AC, Antin JH, Plappert MT, Cook EF, Lee RT. Cyclophosphamide cardiotoxicity in bone marrow transplantation: a prospective evaluation of new dosing regimens. J Clin Oncol. 1991 Jul;9(7):1215-23. doi: 10.1200/JCO.1991.9.7.1215. DOI: https://doi.org/10.1200/JCO.1991.9.7.1215

Gottdiener JS, Appelbaum FR, Ferrans VJ, Deisseroth A, Ziegler J. Cardiotoxicity associated with high-dose cyclophosphamide therapy. Arch Intern Med. 1981 May;141(6):758-63. DOI: https://doi.org/10.1001/archinte.141.6.758

Gollerkeri A, Harrold L, Rose M, Jain D, Burtness BA. Use of paclitaxel in patients with pre-existing cardiomyopathy: a review of our experience. Int J Cancer. 2001 Jul 1;93(1):139-41. doi: 10.1002/ijc.1295. DOI: https://doi.org/10.1002/ijc.1295

Yoon, H.J., Kim, K.H., Kim, H.Y. et al. Impacts of non-recovery of trastuzumab-induced cardiomyopathy on clinical outcomes in patients with breast cancer. Clin Res Cardiol 108, 892–900 (2019) DOI: https://doi.org/10.1007/s00392-019-01417-x

Ohtani K, Fujino T, Ide T, Funakoshi K, Sakamoto I, Hiasa KI, Higo T, Kamezaki K, Akashi K, Tsutsui H. Recovery from left ventricular dysfunction was associated with the early introduction of heart failure medical treatment in cancer patients with anthracycline-induced cardiotoxicity. Clin Res Cardiol. 2019 Jun;108(6):600-611. doi: 10.1007/s00392-018-1386-0. Epub 2018 Oct 26. PMID: 30367208 DOI: https://doi.org/10.1007/s00392-018-1386-0

Esteban-Fernández A, Carvajal Estupiñan JF, Gavira-Gómez JJ, et al. Clinical Profile and Prognosis of a Real-World Cohort of Patients With Moderate or Severe Cancer Therapy-Induced Cardiac Dysfunction. Front Cardiovasc Med. 2021;8:721080. Published 2021 Oct 29. doi:10.3389/fcvm.2021.721080 DOI: https://doi.org/10.3389/fcvm.2021.721080

Zilinyi R, Czompa A, Czegledi A, Gajtko A, Pituk D, Lekli I, et al. The cardioprotective effect ofmetformin in doxorubicin-induced cardiotoxicity: the role of autophagy. Molecules. 2018;23(5):1184. https://doi.org/10.3390/molecules23051184 DOI: https://doi.org/10.3390/molecules23051184

Oh CM, Cho S, Jang JY, KimH, Chun S, ChoiM, et al. Cardioprotective potential of an SGLT2 inhibitor against doxorubicin-induced heart failure. Korean Circ J. 2019;49(12):1183–95. https://doi.org/10.4070/kcj.2019.0180 DOI: https://doi.org/10.4070/kcj.2019.0180

Thackeray JT, Pietzsch S, Stapel B, Ricke-Hoch M, Lee CW, Bankstahl JP, et al. Insulin supplementation attenuates cancer-induced cardiomyopathy and slows tumor disease progression. JCI Insight. 2017;2(10):e93098. https://doi.org/10.1172/jci.insight.93098 DOI: https://doi.org/10.1172/jci.insight.93098

HonorsMA, Kinzig KP. The role of insulin resistance in the development of muscle wasting during cancer cachexia. J Cachexia Sarcopenia Muscle. 2012;3(1):5–11. https://doi.org/10.1007/s13539-011-0051-5. DOI: https://doi.org/10.1007/s13539-011-0051-5