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Published in: Clinical Research in Cardiology 8/2019

01-08-2019 | Anemia | Original Paper

Impacts of non-recovery of trastuzumab-induced cardiomyopathy on clinical outcomes in patients with breast cancer

Authors: Hyun Ju Yoon, Kye Hun Kim, Hyung Yoon Kim, Hyukjin Park, Jae Yeong Cho, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Youngkeun Ahn, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park

Published in: Clinical Research in Cardiology | Issue 8/2019

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Abstract

Objectives

The impacts of non-recovery of trastuzumab-induced left ventricular dysfunction (LVD) on clinical outcomes in breast cancer have been poorly studied. We investigated the predictors of LV-functional non-recovery and its impacts on clinical outcomes in breast cancer patients with trastuzumab-induced LVD.

Methods and results

A total of 243 patients with trastuzumab-induced LVD were divided into the recovered LVD group (n = 195) and non-recovered LVD group (n = 48). Major adverse clinical events (MACEs) including death, symptomatic heart failure (HF), and HF hospitalization (HHF) were compared. Hemoglobin and albumin levels were significantly lower in non-recovered LVD than in recovered LVD group. Non-recovered LVD group showed significantly larger LV end-diastolic and systolic dimension, higher pulmonary artery systolic pressure, lower LV ejection fraction (EF), and decreased global longitudinal strain than in recovered LVD group. Decreased LVEF, enlarged LV size, pulmonary hypertension, and anemia were independent predictors of LV-functional non-recovery. During 45.9 ± 23.5 months of follow-up, MACEs were developed in 32 patients: 15 deaths, 28 symptomatic HF, and 22 HHF. In Kaplan–Meier survival analysis, MACE free survival was significantly lower in non-recovered LVD group than in recovered LVD group (log rank p = 0.002).

Conclusion

LV-functional non-recovery was not uncommon in breast cancer patients with trastuzumab-induced cardiomyopathy, and non-recovered LVD was significantly associated with MACEs. Decreased LVEF, enlarged LV size, pulmonary hypertension, and anemia were independent predictors of LV-functional non-recovery. Careful monitoring for MACEs and intensive medical management should be considered in trastuzumab-induced cardiomyopathy with these characteristics.
Literature
1.
go back to reference Yeh ET, Bickford CL (2009) Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 53:2231–2247CrossRefPubMed Yeh ET, Bickford CL (2009) Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J Am Coll Cardiol 53:2231–2247CrossRefPubMed
2.
go back to reference Minami M, Matsumoto S, Horiuchi H (2010) Cardiovascular side-effects of modern cancer therapy. Circ J 74:1779–1786CrossRefPubMed Minami M, Matsumoto S, Horiuchi H (2010) Cardiovascular side-effects of modern cancer therapy. Circ J 74:1779–1786CrossRefPubMed
3.
go back to reference Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin. Cancer 97:2869–2879CrossRefPubMed Swain SM, Whaley FS, Ewer MS (2003) Congestive heart failure in patients treated with doxorubicin. Cancer 97:2869–2879CrossRefPubMed
4.
go back to reference Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira P, Piccart-Gebhart MJ (2007) HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomized controlled trial. Lancet 369:29–36CrossRefPubMed Smith I, Procter M, Gelber RD, Guillaume S, Feyereislova A, Dowsett M, Goldhirsch A, Untch M, Mariani G, Baselga J, Kaufmann M, Cameron D, Bell R, Bergh J, Coleman R, Wardley A, Harbeck N, Lopez RI, Mallmann P, Gelmon K, Wilcken N, Wist E, Sánchez Rovira P, Piccart-Gebhart MJ (2007) HERA study team. 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomized controlled trial. Lancet 369:29–36CrossRefPubMed
5.
go back to reference Pegram M, Liao J (2012) Trastuzumab treatment in multiple lines: current data and future directions. Clin Breast Cancer 12:10–18CrossRefPubMed Pegram M, Liao J (2012) Trastuzumab treatment in multiple lines: current data and future directions. Clin Breast Cancer 12:10–18CrossRefPubMed
6.
go back to reference Zeglinski M, Ludke A, Jassal DS, Singal PK (2011) Trastuzumabinduced cardiac dysfunction: a ‘dual-hit’. Exp Clin Cardiol 16:70–74PubMedPubMedCentral Zeglinski M, Ludke A, Jassal DS, Singal PK (2011) Trastuzumabinduced cardiac dysfunction: a ‘dual-hit’. Exp Clin Cardiol 16:70–74PubMedPubMedCentral
7.
go back to reference Albini A, Cesana E, Donatelli F, Cammarota R, Bucci EO, Baravelli M, Anzà C, Noonan DM (2011) Cardio-oncology in targeting the HER receptor family: the puzzle of different cardiotoxicities of HER2 inhibitors. Future Cardiol 7:93–704CrossRef Albini A, Cesana E, Donatelli F, Cammarota R, Bucci EO, Baravelli M, Anzà C, Noonan DM (2011) Cardio-oncology in targeting the HER receptor family: the puzzle of different cardiotoxicities of HER2 inhibitors. Future Cardiol 7:93–704CrossRef
9.
go back to reference Perez EA, Rodeheffer R (2004) Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22:322–329CrossRefPubMed Perez EA, Rodeheffer R (2004) Clinical cardiac tolerability of trastuzumab. J Clin Oncol 22:322–329CrossRefPubMed
11.
go back to reference Fiuza M (2009) Cardiotoxicity associated with trastuzumab treatment of HER2 + breast cancer. Adv Ther 26:S9–S17CrossRefPubMed Fiuza M (2009) Cardiotoxicity associated with trastuzumab treatment of HER2 + breast cancer. Adv Ther 26:S9–S17CrossRefPubMed
12.
go back to reference Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Eng J Med 344:783–792CrossRef Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Eng J Med 344:783–792CrossRef
14.
go back to reference Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N (2003) The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165–4174CrossRefPubMed Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, Margolese R, Theoret H, Soran A, Wickerham DL, Wolmark N (2003) The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165–4174CrossRefPubMed
15.
go back to reference Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2 positive breast cancer. N Engl J Med 365:1273–1283CrossRefPubMedPubMedCentral Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, Mackey J, Glaspy J, Chan A, Pawlicki M, Pinter T, Valero V, Liu MC, Sauter G, von Minckwitz G, Visco F, Bee V, Buyse M, Bendahmane B, Tabah-Fisch I, Lindsay MA, Riva A, Crown J, Breast Cancer International Research Group (2011) Adjuvant trastuzumab in HER2 positive breast cancer. N Engl J Med 365:1273–1283CrossRefPubMedPubMedCentral
16.
go back to reference Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL (2009) Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol 27:5685–5692CrossRefPubMed Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R, Utriainen T, Turpeenniemi-Hujanen T, Jyrkkiö S, Möykkynen K, Helle L, Ingalsuo S, Pajunen M, Huusko M, Salminen T, Auvinen P, Leinonen H, Leinonen M, Isola J, Kellokumpu-Lehtinen PL (2009) Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol 27:5685–5692CrossRefPubMed
17.
go back to reference Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. 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;28:1–39CrossRefPubMed Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. 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;28:1–39CrossRefPubMed
18.
go back to reference Marwick TH, Leano RL, Brown J, Sun JP, Hoffmann R, Lysyansky P et al (2009) Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging 2:80–84CrossRefPubMed Marwick TH, Leano RL, Brown J, Sun JP, Hoffmann R, Lysyansky P et al (2009) Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range. JACC Cardiovasc Imaging 2:80–84CrossRefPubMed
19.
go back to reference Martin M, Esteva FJ, Alba E, Khandheria B, Perez-Isla L, Garcia-Saenz JA, Márquez A, Sengupta P, Zamorano J (2009) Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations. Oncologist 14:1–11CrossRefPubMed Martin M, Esteva FJ, Alba E, Khandheria B, Perez-Isla L, Garcia-Saenz JA, Márquez A, Sengupta P, Zamorano J (2009) Minimizing cardiotoxicity while optimizing treatment efficacy with trastuzumab: review and expert recommendations. Oncologist 14:1–11CrossRefPubMed
20.
go back to reference Cappellini MD, Motta I (2015) Anemia in clinical practice-definition and classification: does hemoglobin change with aging? Semin Hematol 52:261–269CrossRefPubMed Cappellini MD, Motta I (2015) Anemia in clinical practice-definition and classification: does hemoglobin change with aging? Semin Hematol 52:261–269CrossRefPubMed
21.
go back to reference Onitilo AA, Engel JM, Stankowski RV (2014) Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf 5:154–166CrossRefPubMedPubMedCentral Onitilo AA, Engel JM, Stankowski RV (2014) Cardiovascular toxicity associated with adjuvant trastuzumab therapy: prevalence, patient characteristics, and risk factors. Ther Adv Drug Saf 5:154–166CrossRefPubMedPubMedCentral
22.
go back to reference Erickson SL, O’Shea KS, Ghaboosi N, Loverro L, Frantz G, Bauer M, Lu LH, Moore MW (1997) ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development 124:4999–5011PubMed Erickson SL, O’Shea KS, Ghaboosi N, Loverro L, Frantz G, Bauer M, Lu LH, Moore MW (1997) ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development 124:4999–5011PubMed
23.
go back to reference Riccio G, Coppola C, Piscopo G, Capasso I, Maurea C, Esposito E, De Lorenzo C, Maurea N (2016) Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I from Type II cardiomyopathies? Hum Vaccin Immunother 12:1124–1131CrossRefPubMedPubMedCentral Riccio G, Coppola C, Piscopo G, Capasso I, Maurea C, Esposito E, De Lorenzo C, Maurea N (2016) Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I from Type II cardiomyopathies? Hum Vaccin Immunother 12:1124–1131CrossRefPubMedPubMedCentral
24.
go back to reference Ohtani K, Fujino T, Ide T, Funakoshi K, Sakamoto I, Hiasa KI, Higo T, Kamezaki K, Akashi K, Tsutsui H (2018) 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 (Epub ahead of print) Ohtani K, Fujino T, Ide T, Funakoshi K, Sakamoto I, Hiasa KI, Higo T, Kamezaki K, Akashi K, Tsutsui H (2018) 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 (Epub ahead of print)
25.
go back to reference Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, Allen LA, Nekhlyudov L, Goddard KA, Davis RL, Habel LA, Yood MU, McCarty C, Magid DJ, Wagner EH, Pharmacovigilance Study Team (2012) Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst 104:1293–1305CrossRefPubMedPubMedCentral Bowles EJ, Wellman R, Feigelson HS, Onitilo AA, Freedman AN, Delate T, Allen LA, Nekhlyudov L, Goddard KA, Davis RL, Habel LA, Yood MU, McCarty C, Magid DJ, Wagner EH, Pharmacovigilance Study Team (2012) Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst 104:1293–1305CrossRefPubMedPubMedCentral
26.
go back to reference Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP (2012) Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol 60:2504–2512CrossRefPubMed Chen J, Long JB, Hurria A, Owusu C, Steingart RM, Gross CP (2012) Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol 60:2504–2512CrossRefPubMed
27.
go back to reference Yoon HJ, Kim KH, Kim JY, Park HJ, Cho JY, Hong YJ, Park HW, Kim JH, Ahn Y, Jeong MH, Cho JG, Park JC (2016) Chemotherapy-induced left ventricular dysfunction in patients with breast cancer. J Breast Cancer 19:402–409CrossRefPubMedPubMedCentral Yoon HJ, Kim KH, Kim JY, Park HJ, Cho JY, Hong YJ, Park HW, Kim JH, Ahn Y, Jeong MH, Cho JG, Park JC (2016) Chemotherapy-induced left ventricular dysfunction in patients with breast cancer. J Breast Cancer 19:402–409CrossRefPubMedPubMedCentral
28.
go back to reference Szachniewicz J, Petruk-Kowalczyk J, Majda J, Kaczmarek A, Reczuch K, Kalra PR, Piepoli MF, Anker SD, Banasiak W, Ponikowski P (2003) Anemia is an independent predictor of pooroutcome in patients with chronic heart failure. Int J Cardiol 90:303–308CrossRefPubMed Szachniewicz J, Petruk-Kowalczyk J, Majda J, Kaczmarek A, Reczuch K, Kalra PR, Piepoli MF, Anker SD, Banasiak W, Ponikowski P (2003) Anemia is an independent predictor of pooroutcome in patients with chronic heart failure. Int J Cardiol 90:303–308CrossRefPubMed
29.
go back to reference Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, Chiang YT, Aknay N, Maggioni AP, Opasich C, Latini R, Cohn JN.et al (2005) Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 112:1121–1127CrossRefPubMed Anand IS, Kuskowski MA, Rector TS, Florea VG, Glazer RD, Hester A, Chiang YT, Aknay N, Maggioni AP, Opasich C, Latini R, Cohn JN.et al (2005) Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation 112:1121–1127CrossRefPubMed
30.
go back to reference Kosiborod M, Smith GL, Radford MJ, Foody JM, Krumholz HM (2003) The prognostic importance of anaemia in patients with heart failure. Am J Med 114:112–119CrossRefPubMed Kosiborod M, Smith GL, Radford MJ, Foody JM, Krumholz HM (2003) The prognostic importance of anaemia in patients with heart failure. Am J Med 114:112–119CrossRefPubMed
Metadata
Title
Impacts of non-recovery of trastuzumab-induced cardiomyopathy on clinical outcomes in patients with breast cancer
Authors
Hyun Ju Yoon
Kye Hun Kim
Hyung Yoon Kim
Hyukjin Park
Jae Yeong Cho
Young Joon Hong
Hyung Wook Park
Ju Han Kim
Youngkeun Ahn
Myung Ho Jeong
Jeong Gwan Cho
Jong Chun Park
Publication date
01-08-2019

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