EARLY CHANGES IN LEFT-VENTRICULAR EJECTION FRACTION AND LONGITUDINAL DEFORMATION IN PATIENTS WITH BREAST CANCER AT ANTHRACYCLINE CONTAINING REGIMENS
Keywords:
anthracyclines, breast cancer, echocardiography, ejection fraction, longitudinal strainAbstract
Background: Anthracyclines (ATs) are the most frequent used anti-cancer drugs in breast cancer (BC) patients. Certain demographic parameters and risk factors are closely linked to anthracycline-induced cardiotoxicity manifestation as the most feared adverse effect.
Aims: The study aimed to assess the differences in selected echocardiographic parameters related to LV systolic function including longitudinal strain (LS%) according to cardiovascular (CV) risk factors and demographic characteristics and their relations in BC patients treated with ATs.
Methods: Thirty patients with newly diagnosed BC scheduled to receive ATs were examined. The following demographic parameters and risk factors were evaluated: age, body mass index, obesity, hypertension, diabetes, physical activity and total AT dose. The echocardiographic evaluation consisted of parameters for LV systolic function estimation, including LV ejection fraction (LVEF%) and LS%. Statistical analysis was done with the SPSS, v.25.0.
Results: LVEF%, GLS%, and LS% in two/four chamber view (A4c/A2c) statistically significantly decreased at the control evaluation (p=0.036, p=0,002, p=0,031, p=0,019). Correlation between the differences in LVEF% between two visits showed a significant relation with the absence of physical activity (p=0,029), while a significant correlation of the LS% decrease was also found in A4c view with diabetes (p=0.024).
Conclusion: ATs initiate frequent echocardiography changes in BC patients. Close monitoring and regular surveillance ensure early diagnosis of serious cardiotoxic complications. Cancer therapy-related cardiac dysfunction (CTRCD) is a broad spectrum of possible presentations, and serial LVEF% and LS% measurement are ideal tools to identify the disease in early, asymptomatic stage and guide further therapeutic strategies.
References
World Health Organization. Breast cancer. 2023. Available at: https://www.who.int/ news-room/fact-sheets/detail/breast-cancer.
Breast Cancer Facts and Statistics. Breast cancer facts and statistics 2023. (accessed 2023, September 30). https://www.breastcancer.org/facts-statistics.
Santoro C, Arpino G, Esposito R, Lembo M, Paciolla I, Cardalesi C, et al. 2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility. Eur Heart J Cardiovasc Imaging 2017; 18(8): 930-936. doi: 10.1 093/ehjci/jex033.
Mouabbi AJ. Breast cancer treatment protocols. Treatment of Noninvasive breast cancer. 2023. Available at: https://emedicine.medscape.com/article/2006464-overview.
Chimed S, Stassen J, Galloo X, Meucci M C, Knuuti J, Delgado V, et al. Prognostic relevance of left ventricular global longitudinal strain in patients with heart failure and reduced ejection fraction. Am J Cardiol 2023; 202: 30-40, doi: 10.1016/j.amjcard. 2023.06.058.
Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with European Hematology Association, European Society for Therapeutic Radiology and Oncology and International Cardio-Oncology Society. Eur Heart J 2022; 43(41): 4229-4361. doi: 10. 1093/eurheartj/ehac244.
Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of Anthracyclines. Front Cardiovasc Med 2020; 7:26. doi: 10.3389/fcvm.2020.00026.
Čelutkienė J, Pudil R, López‐Fernández T, Grapsa J, Nihoyannopoulos P, Bergler-Klein J, et al. Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: A position statement on behalf of the Heart Failure association, European association of Cardiovasc. Imaging and cardio‐oncology Council of ESC. Eur J Heart Fail 2020; 22(9): 1504-1524. doi: 10.1002/ejhf.1957.
Lyon AR, Dent S, Stanway S, Earl H, Brezden-Masley C, Cohen-Solal A, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: A position statement and new risk assessment tools from the Cardio‐Oncology study Group of the Heart Failure Association of the ESC in collaboration with the International Cardio‐ Oncology society. Eur J Heart Fail 2020; 22(11): 1945–1960. doi: 10.1002/ejhf.1920.
Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines. Eur Heart J 2016; 37(36): 2768-2801. doi: 10.1093/eurheartj/ehw211.
Qiu S, Zhou T, Qiu B, Zhang Y, Zhou Y, Yu H, et al. Risk Factors for Anthracycline-Induced Cardiotoxicity. Front Cardiovasc Med 2021; 8: 736854. doi: 10.3389/fcvm. 2021.736854.
Early Breast Cancer Trialists’ Collaborative Group. Comparisons between different polychemotherapy regimens for early breast cancer: Meta-analyses of long-term outcome among 100 000 women in 123 randomised trials. The Lancet 2012; 379(9814): 432-444. doi: 10.1016/S0140-6736(11)61625-5.
Braybrooke J, Bradley R, Gray R, Hills RK, Pan H, Peto R, et al. Anthracycline-containing and Taxane-containing chemotherapy for early-stage operable breast cancer: A patient-level meta-analysis of 100 000 women from 86 randomised trials. The Lancet. 2023; 401(10384): 1277-1292. doi: 10.1016/S0140-6736(23)00285-4.
Lotrionte M, Biondi-Zoccai G, Abbate A, Lanzetta G, D’Ascenzo F, Malavasi V, et al. Review and meta-analysis of incidence and clinical predictors of anthracycline cardiotoxicity. Am J Cardiol 2013; 112(12): 1980-1984. doi: 10.1016/j.amjcard.2013. 08.026.
Sadeq IA, Mohammed MQ, AL-Timimi AA, Al Enbari AA. Detection of subclinical left-ventricular systolic dysfunction in patient treated with anthracycline chemotherapy: A comparative analysis between different left-ventricular systolic echocardiographic parameters. International Journal of Adv Research in Biological Sciences 2019; 6(8): 137-147. doi: http://dx.doi.org/10.22192/ijarbs.2019.06.08.019.
Jeyaprakash P, Sangha S, Ellenberger K, Sivapathan S, Pathan F, Negishi K. Cardiotoxic Effect of Modern Anthracycline Dosing on Left Ventricular Ejection Fraction: A Systematic Review and Meta-Analysis of Placebo Arms From Randomized Controlled Trials. J Am Heart Assoc 2021; 10(6): e018802. doi: 10.1161/JAHA.120.018802.
Boyd A, Stoodley P, Richards D, Hui R, Harnett P, Vo K, et al. Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study. PLoS One 2017; 12(4): e0175544. doi: 10.1371/journal.pone.0175544.
Mehta LS, Watson KE, Barac A, Beckie TM, Bittner V, Cruz-Flores S, et al; American Heart Association Cardiovascular Disease in Women and Special Populations Committee of the Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; and Council on Quality of Care and Outcomes Research. Cardiovascular Disease and Breast Cancer: Where These Entities Intersect: A Scientific Statement From the American Heart Association. Circulation 2018; 137(8): e30-e66. doi: 10.1161/CIR.0000000000000 556.
Screever EM, Meijers WC, Moslehi JJ. Age-Related Considerations in Cardio-Oncology. J Cardiovasc Pharmacol Ther 2021; 26(2): 103-113. doi: 10.1177/1074248420968689.
Cleary MP, Grossmann ME. Minireview: Obesity and breast cancer: the estrogen connection. Endocrinology 2009; 150(6): 2537-42. doi: 10.1210/en.2009-0070.
Guenancia C, Lefebvre A, Cardinale D, Yu AF, Ladoire S, Ghiringhelli F, et al. Obesity As a Risk Factor for Anthracyclines and Trastuzumab Cardiotoxicity in Breast Cancer: A Systematic Review and Meta-Analysis. J Clin Oncol 2016; 34(26): 3157-3165. doi: 10.120 0/JCO.2016.67.4846.
de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JPA, Vicente M, et al. The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: The experience of 02-98 trial. Breast Cancer Res Treat 2009; 119(1): 145-153. doi: 10.1007/s10549-009-0512-0.
Reding KW, Ghemigian K, Carbone S, D’Agostino RJr, Jordan JH, Melendez G, et al. The relationship between abdominal fat and change in left-ventricular ejection fraction in cancer patients. Obes Sci Pract 2020; 7(1): 82-90. doi: 10.1002/osp4.454.
Kotwinski P, Smith G, Cooper J, Sanders J, Ma L, Teis A, et al. Body Surface Area and Baseline Blood Pressure Predict Subclinical Anthracycline Cardiotoxicity in Women Treated for Early Breast Cancer. PLoS One 2016; 11(12): e0165262. doi: 10.1371/ journal.pone.0165262.
Philip LJ, Findlay SG, Gill JH. Baseline blood pressure and development of cardiotoxicity in patients treated with anthracyclines: A systematic review. Int J Cardiol Cardiovasc Risk Prev 2022; 15: 200153. doi: 10.1016/j.ijcrp.2022.200153.
Reinbolt RE, Patel R, Pan X, Timmers CD, Pilarski R, Shapiro CL, et al. Risk factors for anthracycline-associated cardiotoxicity. Support Care Cancer 2016; 24(5): 2173-2180. doi: 10.1007/s00520-015-3008-y.
Zhang M, Yang H, Xu C, Jin F, Zheng A. Risk Factors for Anthracycline-Induced Cardiotoxicity in Breast Cancer Treatment: A Meta-Analysis. Front Oncol 2022; 12: 899782. doi: 10.3389/fonc.2022.899782.
Kang DW, Wilson RL, Christopher CN, Normann AJ, Barnes O, Lesansee JD, et al. Exercise Cardio-Oncology: Exercise as a Potential Therapeutic Modality in the Management of Anthracycline-Induced Cardiotoxicity. Front Cardiovasc Med 2022; 8: 805735. doi: 10.3389/fcvm.2021.805735.
Antunes P, Esteves D, Nunes C, Amarelo A, Fonseca-Moutinho J, Afreixo V, et al. Effects of exercise on cardiac function outcomes in women receiving anthracycline or trastuzumab treatment for breast cancer: A systematic review and meta-analysis. Applied Sciences 2021; 11(18): 8336. https://doi.org/10.3390/app11188336.
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28(1): 1-39.e14. doi: 10.1016/j.echo.2014. 10.003.
