Pharmacovigilance Study: Evaluating Anthracycline Induced Cardiotoxicity Through Echocardiography in Breast Cancer Patients at Dr. Kariadi Hospital
DOI:
https://doi.org/10.22146/ijp.20889Keywords:
Anthracycline, cardiotoxicity, breast cancer, echocardiography, left ventricular ejection fraction (LVEF)Abstract
Anthracycline-based chemotherapy, including doxorubicin and epirubicin, is widely used in breast cancer treatment but is associated with anthracycline-induced cardiotoxicity (AIC), which may lead to left ventricular dysfunction. This study evaluates AIC in breast cancer patients by assessing left ventricular ejection fraction (LVEF) changes following anthracycline therapy. This retrospective cross-sectional study included 68 female outpatients diagnosed with primary breast cancer who received anthracycline chemotherapy at Dr. Kariadi Hospital from 2022 to 2024. LVEF was assessed via echocardiography before and after treatment. Cardiotoxicity was defined as an LVEF decline of ≥10% from baseline. Statistical analysis was performed using SPSS version 20, with a p-value <0.05 considered significant. Cardiotoxicity occurred in 32.4% of patients, but statistical analysis (P = 0.298) revealed no significant association between anthracycline administration and LVEF reduction. Additionally, no significant correlations were found between LVEF decline and age (P = 0.236), body mass index (P = 0.954), comorbidities (P = 0.196), anthracycline type (P = 0.601), chemotherapy cycles (P = 0.735), cancer stage (P = 0.208), or cumulative dose (P = 0.061). Although cardiotoxicity was observed in some patients, no statistically significant decline in LVEF was detected. Further studies with larger cohorts and extended follow-ups are needed to assess long-term cardiac effects and optimize cardiotoxicity monitoring strategies.
References
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Ichida, M., Kataoka, A., Tsushima, R., & Taguchi, T. (2015). No increase in breast cancer risk in Japanese women taking oral contraceptives: A case-control study investigating reproductive, menstrual and familial risk factors for breast cancer. Asian Pacific Journal of Cancer Prevention, 16(9), 3685–3690. https://doi.org/10.7314/APJCP.2015.16.9.3685
Kim, D. S., & Scherer, P. E. (2021). Obesity, diabetes, and increased cancer progression. Diabetes and Metabolism Journal, 45(6), 799–812. https://doi.org/10.4093/dmj.2021.0077
Landstrom, A. P., Dobrev, D., & Wehrens, X. H. T. (2017). Calcium Signaling and Cardiac Arrhythmias. Circulation Research, 120(12), 1969–1993. https://doi.org/10.1161/CIRCRESAHA.117.310083
Li, H., Wang, M., & Huang, Y. (2024). Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective. In Biomedicine and Pharmacotherapy (Vol. 179). Elsevier Masson s.r.l. https://doi.org/10.1016/j.biopha.2024.117312
Mao, X., Wu, S., Huang, D., & Li, C. (2024). Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy. Acta Pharmaceutica Sinica B, 14(7), 2901–2926. https://doi.org/10.1016/j.apsb.2024.03.006
Murabito, A., Hirsch, E., & Ghigo, A. (2020). Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer? Frontiers in Cardiovascular Medicine, 7(March), 1–12. https://doi.org/10.3389/fcvm.2020.00035
Özbay, B., Şimşek, E., Kemal, H., Çakar, B., & Yavuzgil, O. (2022). Anthracycline Chemotherapy-Induced Electro-Mechanical Changes: Strain Echocardiography Combined with Repolarization Parameters on Electrocardiography to Predict Early Cardiotoxicity. Turk Kardiyoloji Dernegi Arsivi, 50(7), 478–484. https://doi.org/10.5543/tkda.2022.22359
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia. (2021). Panduan Pemeriksaan Ekokardiografi di Klinik.
Philip, L. J., Findlay, S. G., & Gill, J. H. (2022). Baseline blood pressure and development of cardiotoxicity in patients treated with anthracyclines: A systematic review: Baseline Blood Pressure and Anthracycline-Associated Cardiotoxicity. International Journal of Cardiology: Cardiovascular Risk and Prevention, 15. https://doi.org/10.1016/j.ijcrp.2022.200153
Picon‐Ruiz, M., Morata‐Tarifa, C., Valle‐Goffin, J. J., Friedman, E. R., & Slingerland, J. M. (2017). Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA: A Cancer Journal for Clinicians, 67(5), 378–397. https://doi.org/10.3322/caac.21405
Qiu, S., Zhou, T., Qiu, B., Zhang, Y., Zhou, Y., Yu, H., Zhang, J., Liu, L., Yuan, L., Yang, G., Duan, Y., & Xing, C. (2021). Risk Factors for Anthracycline-Induced Cardiotoxicity. Frontiers in Cardiovascular Medicine, 8(September), 1–12. https://doi.org/10.3389/fcvm.2021.736854
Ramteke, P., Deb, A., Shepal, V., & Bhat, M. K. (2019). Hyperglycemia associated metabolic and molecular alterations in cancer risk, progression, treatment, and mortality. In Cancers (Vol. 11, Issue 9). MDPI AG. https://doi.org/10.3390/cancers11091402
Tursunova, N. V., Klinnikova, M. G., Babenko, O. A., & Lushnikova, E. L. (2021). Molecular Mechanisms of the Cardiotoxic Action of Anthracycline Antibiotics and Statin-Induced Cytoprotective Reactions of Cardiomyocytes. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 15(2), 89–104. https://doi.org/10.1134/S1990750821020116
Tzimas, C., Johnson, D. M., Santiago, D. J., Vafiadaki, E., Arvanitis, D. A., Davos, C. H., Varela, A., Athanasiadis, N. C., Dimitriou, C., Katsimpoulas, M., Sonntag, S., Kryzhanovska, M., Shmerling, D., Lehnart, S. E., Sipido, K. R., Kranias, E. G., & Sanoudou, D. (2017). Impaired calciumhomeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalentmouse model of the human HRC-Ser96Ala variant. Cardiovascular Research, 113(11), 1403–1417. https://doi.org/10.1093/cvr/cvx113
World Health Organization. (2023). Breast Cancer. https://www.who.int/news-room/fact-sheets/detail/breast-cancer
Yang, Z., Chen, Y., Liu, X., Cui, J., Hu, Y., & Wei, W. (2020). Effects of adjuvant chemotherapy on recurrence rate in T1abN0M0 triple-negative breast cancer: A meta-analysis. Cancer Treatment and Research Communications, 25(September), 100211. https://doi.org/10.1016/j.ctarc.2020.100211
Zamorano, J. L., Lancellotti, P., Rodriguez Muñoz, D., Aboyans, V., Asteggiano, R., Galderisi, M., Habib, G., Lenihan, D. J., Lip, G. Y. H., Lyon, A. R., Lopez Fernandez, T., Mohty, D., Piepoli, M. F., Tamargo, J., Torbicki, A., Suter, T. M., Achenbach, S., Agewall, S., Badimon, L., Szmit, S. (2016). 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. European Heart Journal, 37(36), 2768–2801. https://doi.org/10.1093/eurheartj/ehw211
Zhang, A. M. Y., Wellberg, E. A., Kopp, J. L., & Johnson, J. D. (2021). Hyperinsulinemia in obesity, inflammation, and cancer. Diabetes and Metabolism Journal, 45(3), 285–311. https://doi.org/10.4093/DMJ.2020.0250
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394–424. https://doi.org/10.3322/caac.21492
Cardinale, D., Colombo, A., Bacchiani, G., Tedeschi, I., Meroni, C. A., Veglia, F., Civelli, M., Lamantia, G., Colombo, N., Curigliano, G., Fiorentini, C., & Cipolla, C. M. (2015). Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy. Circulation, 131(22), 1981–1988. https://doi.org/10.1161/CIRCULATIONAHA.114.013777
Conway, J. R. W., Dinç, D. D., Follain, G., Paavolainen, O., Kaivola, J., Boström, P., Hartiala, P., Peuhu, E., & Ivaska, J. (2023). IGFBP2 secretion by mammary adipocytes limits breast cancer invasion. Science Advances, 9(28), 1–15. https://doi.org/10.1126/sciadv.adg1840
Curigliano, G., Cardinale, D., Dent, S., Criscitiello, C., Aseyev, O., Lenihan, D., & Cipolla, C. M. (2016). Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management. CA: A Cancer Journal for Clinicians, 66(4), 309–325. https://doi.org/10.3322/caac.21341
Divella, R., De Luca, R., Abbate, I., Naglieri, E., & Daniele, A. (2016). Obesity and cancer: The role of adipose tissue and adipo-cytokines-induced chronic inflammation. In Journal of Cancer (Vol. 7, Issue 15, pp. 2346–2359). Ivyspring International Publisher. https://doi.org/10.7150/jca.16884
Engin, A. B., & Engin, A. (2017). Obesity and Lipotoxicity (Vol. 960). https://doi.org/10.1007/978-3-319-48382-5
Fidler-Benaoudia, M. M., Heer, E., Harper, A., Escandor, N., Sung, H., & McCormack, V. (2020). Global burden and trends in premenopausal and postmenopausal breast cancer: a population-based study. In Articles Lancet Glob Health (Vol. 8). www.thelancet.com/lancetgh
Gerodias, F. R., Tan, M. K., De Guzman, A., Bernan, A., Locnen, S. A., Apostol-Alday, A., Ybanez, E. J., Magno, J. D., Lim, A., Junia, A., Mambulao, R., Cosare-San Pedro, J., Lucero, J., Quijano, Z., Apurillo, J., Uson, A. J., Lim, J. L., Inso, C. A., Agoncillo-Infante, A., Gumapon, J. K. (2022). Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients: A Five-Year Retrospective Study in 10 Centers. Cardiology Research, 13(6), 380–392. https://doi.org/10.14740/cr1442
Gradishar, W. J., Moran, M. S., Abraham, J., Abramson, V., Aft, R., Agnese, D., Allison, K. H., Anderson, B., Bailey, J., Burstein, H. J., Chen, N., Chew, H., Dang, C., Elias, A. D., Giordano, S. H., Goetz, M. P., Jankowitz, R. C., Javid, S. H., Krishnamurthy, J., Kumar, R. (2024). Breast Cancer, Version 3.2024. JNCCN Journal of the National Comprehensive Cancer Network, 22(5), 331–357. https://doi.org/10.6004/jnccn.2024.0035
Guarneri, V., & de Azambuja, E. (2022). Anthracyclines in the treatment of patients with early breast cancer. ESMO Open, 7(3), 100461. https://doi.org/10.1016/j.esmoop.2022.100461
Ichida, M., Kataoka, A., Tsushima, R., & Taguchi, T. (2015). No increase in breast cancer risk in Japanese women taking oral contraceptives: A case-control study investigating reproductive, menstrual and familial risk factors for breast cancer. Asian Pacific Journal of Cancer Prevention, 16(9), 3685–3690. https://doi.org/10.7314/APJCP.2015.16.9.3685
Kim, D. S., & Scherer, P. E. (2021). Obesity, diabetes, and increased cancer progression. Diabetes and Metabolism Journal, 45(6), 799–812. https://doi.org/10.4093/dmj.2021.0077
Landstrom, A. P., Dobrev, D., & Wehrens, X. H. T. (2017). Calcium Signaling and Cardiac Arrhythmias. Circulation Research, 120(12), 1969–1993. https://doi.org/10.1161/CIRCRESAHA.117.310083
Li, H., Wang, M., & Huang, Y. (2024). Anthracycline-induced cardiotoxicity: An overview from cellular structural perspective. In Biomedicine and Pharmacotherapy (Vol. 179). Elsevier Masson s.r.l. https://doi.org/10.1016/j.biopha.2024.117312
Mao, X., Wu, S., Huang, D., & Li, C. (2024). Complications and comorbidities associated with antineoplastic chemotherapy: Rethinking drug design and delivery for anticancer therapy. Acta Pharmaceutica Sinica B, 14(7), 2901–2926. https://doi.org/10.1016/j.apsb.2024.03.006
Murabito, A., Hirsch, E., & Ghigo, A. (2020). Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer? Frontiers in Cardiovascular Medicine, 7(March), 1–12. https://doi.org/10.3389/fcvm.2020.00035
Özbay, B., Şimşek, E., Kemal, H., Çakar, B., & Yavuzgil, O. (2022). Anthracycline Chemotherapy-Induced Electro-Mechanical Changes: Strain Echocardiography Combined with Repolarization Parameters on Electrocardiography to Predict Early Cardiotoxicity. Turk Kardiyoloji Dernegi Arsivi, 50(7), 478–484. https://doi.org/10.5543/tkda.2022.22359
Perhimpunan Dokter Spesialis Kardiovaskular Indonesia. (2021). Panduan Pemeriksaan Ekokardiografi di Klinik.
Philip, L. J., Findlay, S. G., & Gill, J. H. (2022). Baseline blood pressure and development of cardiotoxicity in patients treated with anthracyclines: A systematic review: Baseline Blood Pressure and Anthracycline-Associated Cardiotoxicity. International Journal of Cardiology: Cardiovascular Risk and Prevention, 15. https://doi.org/10.1016/j.ijcrp.2022.200153
Picon‐Ruiz, M., Morata‐Tarifa, C., Valle‐Goffin, J. J., Friedman, E. R., & Slingerland, J. M. (2017). Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA: A Cancer Journal for Clinicians, 67(5), 378–397. https://doi.org/10.3322/caac.21405
Qiu, S., Zhou, T., Qiu, B., Zhang, Y., Zhou, Y., Yu, H., Zhang, J., Liu, L., Yuan, L., Yang, G., Duan, Y., & Xing, C. (2021). Risk Factors for Anthracycline-Induced Cardiotoxicity. Frontiers in Cardiovascular Medicine, 8(September), 1–12. https://doi.org/10.3389/fcvm.2021.736854
Ramteke, P., Deb, A., Shepal, V., & Bhat, M. K. (2019). Hyperglycemia associated metabolic and molecular alterations in cancer risk, progression, treatment, and mortality. In Cancers (Vol. 11, Issue 9). MDPI AG. https://doi.org/10.3390/cancers11091402
Tursunova, N. V., Klinnikova, M. G., Babenko, O. A., & Lushnikova, E. L. (2021). Molecular Mechanisms of the Cardiotoxic Action of Anthracycline Antibiotics and Statin-Induced Cytoprotective Reactions of Cardiomyocytes. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 15(2), 89–104. https://doi.org/10.1134/S1990750821020116
Tzimas, C., Johnson, D. M., Santiago, D. J., Vafiadaki, E., Arvanitis, D. A., Davos, C. H., Varela, A., Athanasiadis, N. C., Dimitriou, C., Katsimpoulas, M., Sonntag, S., Kryzhanovska, M., Shmerling, D., Lehnart, S. E., Sipido, K. R., Kranias, E. G., & Sanoudou, D. (2017). Impaired calciumhomeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalentmouse model of the human HRC-Ser96Ala variant. Cardiovascular Research, 113(11), 1403–1417. https://doi.org/10.1093/cvr/cvx113
World Health Organization. (2023). Breast Cancer. https://www.who.int/news-room/fact-sheets/detail/breast-cancer
Yang, Z., Chen, Y., Liu, X., Cui, J., Hu, Y., & Wei, W. (2020). Effects of adjuvant chemotherapy on recurrence rate in T1abN0M0 triple-negative breast cancer: A meta-analysis. Cancer Treatment and Research Communications, 25(September), 100211. https://doi.org/10.1016/j.ctarc.2020.100211
Zamorano, J. L., Lancellotti, P., Rodriguez Muñoz, D., Aboyans, V., Asteggiano, R., Galderisi, M., Habib, G., Lenihan, D. J., Lip, G. Y. H., Lyon, A. R., Lopez Fernandez, T., Mohty, D., Piepoli, M. F., Tamargo, J., Torbicki, A., Suter, T. M., Achenbach, S., Agewall, S., Badimon, L., Szmit, S. (2016). 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. European Heart Journal, 37(36), 2768–2801. https://doi.org/10.1093/eurheartj/ehw211
Zhang, A. M. Y., Wellberg, E. A., Kopp, J. L., & Johnson, J. D. (2021). Hyperinsulinemia in obesity, inflammation, and cancer. Diabetes and Metabolism Journal, 45(3), 285–311. https://doi.org/10.4093/DMJ.2020.0250
Published
2026-06-25
How to Cite
Budijitno, S., Alwi, L., Dilaga, A. A., Savitri, A. A., Palgunadi, Swastifa, N. N., Amaliah, R. R., & Ahmad, A. P. (2026). Pharmacovigilance Study: Evaluating Anthracycline Induced Cardiotoxicity Through Echocardiography in Breast Cancer Patients at Dr. Kariadi Hospital. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.20889
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Research Article
