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Published in: Targeted Oncology 4/2011

01-12-2011 | Review

Heart to heart with trastuzumab: a review on cardiac toxicity

Author: Serena Di Cosimo

Published in: Targeted Oncology | Issue 4/2011

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Abstract

Trastuzumab is regarded as the foundation of care for HER2-positive breast cancer as it has revolutionized the treatment of this disease across all settings. Although generally well tolerated, patients may develop symptomatic or asymptomatic cardiotoxicity, forcing a discontinuation of treatment, therefore preventing patients from benefiting from maximal disease control. Evolving research supports that trastuzumab-induced cardiotoxicity may be prevented or at least minimized by a number of prophylactic measures, such as identification of patients at risk and close monitoring. Optimized chemotherapy regimens, scheduling and formulations also contribute to minimizing cardiac adverse events. Equally important, if cardiotoxicity develops, medical interventions are now available that facilitate the reintroduction of trastuzumab once normal cardiac function has been restored. Awareness of this still-evolving information may lead to optimal use of trastuzumab, especially in combination regimens, maximizing antitumor benefit, while minimizing risk.
Literature
2.
go back to reference Carter P et al (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 89(10):4285–4289PubMedCrossRef Carter P et al (1992) Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc Natl Acad Sci U S A 89(10):4285–4289PubMedCrossRef
3.
go back to reference Slamon DJ et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792PubMedCrossRef Slamon DJ et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792PubMedCrossRef
4.
go back to reference Marty M et al (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23(19):4265–4274PubMedCrossRef Marty M et al (2005) Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group. J Clin Oncol 23(19):4265–4274PubMedCrossRef
5.
go back to reference Baselga J et al (1996) Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 14(3):737–744PubMed Baselga J et al (1996) Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 14(3):737–744PubMed
6.
go back to reference Vogel CL et al (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719–726PubMedCrossRef Vogel CL et al (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20(3):719–726PubMedCrossRef
7.
go back to reference Dahabreh IJ et al (2008) Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist 13(6):620–630PubMedCrossRef Dahabreh IJ et al (2008) Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist 13(6):620–630PubMedCrossRef
8.
go back to reference Gianni L et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 375(9712):377–384PubMedCrossRef Gianni L et al (2010) Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet 375(9712):377–384PubMedCrossRef
9.
go back to reference Russell SD et al (2010) Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials. J Clin Oncol 28(21):3416–3421PubMedCrossRef Russell SD et al (2010) Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 clinical trials. J Clin Oncol 28(21):3416–3421PubMedCrossRef
10.
go back to reference Smith LA et al (2010) Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 10:337PubMedCrossRef Smith LA et al (2010) Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 10:337PubMedCrossRef
11.
12.
go back to reference Viani GA et al (2007) Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer 7:153PubMedCrossRef Viani GA et al (2007) Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer 7:153PubMedCrossRef
13.
go back to reference Ozcelik C et al (2002) Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proc Natl Acad Sci U S A 99(13):8880–8885PubMedCrossRef Ozcelik C et al (2002) Conditional mutation of the ErbB2 (HER2) receptor in cardiomyocytes leads to dilated cardiomyopathy. Proc Natl Acad Sci U S A 99(13):8880–8885PubMedCrossRef
14.
go back to reference Crone SA et al (2002) ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8(5):459–465PubMedCrossRef Crone SA et al (2002) ErbB2 is essential in the prevention of dilated cardiomyopathy. Nat Med 8(5):459–465PubMedCrossRef
15.
go back to reference Lemmens K, Doggen K, De Keulenaer GW (2007) Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure. Circulation 116(8):954–960PubMedCrossRef Lemmens K, Doggen K, De Keulenaer GW (2007) Role of neuregulin-1/ErbB signaling in cardiovascular physiology and disease: implications for therapy of heart failure. Circulation 116(8):954–960PubMedCrossRef
16.
go back to reference Liu X et al (2006) Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. J Am Coll Cardiol 48(7):1438–1447PubMedCrossRef Liu X et al (2006) Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy. J Am Coll Cardiol 48(7):1438–1447PubMedCrossRef
17.
go back to reference Romond EH et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684PubMedCrossRef Romond EH et al (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353(16):1673–1684PubMedCrossRef
18.
go back to reference Piccart-Gebhart MJ et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672PubMedCrossRef Piccart-Gebhart MJ et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353(16):1659–1672PubMedCrossRef
19.
go back to reference Baselga J et al (1998) Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 58(13):2825–2831PubMed Baselga J et al (1998) Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 58(13):2825–2831PubMed
20.
go back to reference Jarvinen TA, Liu ET (2000) Effects of HER-2/neu on chemosensitivity of tumor cells. Drug Resist Updat 3(6):319–324PubMedCrossRef Jarvinen TA, Liu ET (2000) Effects of HER-2/neu on chemosensitivity of tumor cells. Drug Resist Updat 3(6):319–324PubMedCrossRef
21.
go back to reference Bianchi G et al (2003) Pilot trial of trastuzumab starting with or after the doxorubicin component of a doxorubicin plus paclitaxel regimen for women with HER2-positive advanced breast cancer. Clin Cancer Res 9(16 Pt 1):5944–5951PubMed Bianchi G et al (2003) Pilot trial of trastuzumab starting with or after the doxorubicin component of a doxorubicin plus paclitaxel regimen for women with HER2-positive advanced breast cancer. Clin Cancer Res 9(16 Pt 1):5944–5951PubMed
22.
go back to reference Untch M et al (2010) Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 28(12):2024–2031PubMedCrossRef Untch M et al (2010) Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol 28(12):2024–2031PubMedCrossRef
23.
go back to reference Harris L et al (2002) Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 94(1):25–36PubMedCrossRef Harris L et al (2002) Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 94(1):25–36PubMedCrossRef
24.
go back to reference Batist G et al (2001) Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol 19(5):1444–1454PubMed Batist G et al (2001) Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol 19(5):1444–1454PubMed
25.
go back to reference Cortes J et al (2009) Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study. Clin Cancer Res 15(1):307–314PubMedCrossRef Cortes J et al (2009) Nonpegylated liposomal doxorubicin (TLC-D99), paclitaxel, and trastuzumab in HER-2-overexpressing breast cancer: a multicenter phase I/II study. Clin Cancer Res 15(1):307–314PubMedCrossRef
26.
go back to reference Chia S et al (2006) Pegylated liposomal doxorubicin and trastuzumab in HER-2 overexpressing metastatic breast cancer: a multicenter phase II trial. J Clin Oncol 24(18):2773–2778PubMedCrossRef Chia S et al (2006) Pegylated liposomal doxorubicin and trastuzumab in HER-2 overexpressing metastatic breast cancer: a multicenter phase II trial. J Clin Oncol 24(18):2773–2778PubMedCrossRef
27.
go back to reference de la Fouchardiere C et al (2009) Docetaxel and pegylated liposomal doxorubicin combination as first-line therapy for metastatic breast cancer patients: results of the phase II GINECO trial CAPYTTOLE. Ann Oncol 20(12):1959–1963PubMedCrossRef de la Fouchardiere C et al (2009) Docetaxel and pegylated liposomal doxorubicin combination as first-line therapy for metastatic breast cancer patients: results of the phase II GINECO trial CAPYTTOLE. Ann Oncol 20(12):1959–1963PubMedCrossRef
28.
go back to reference Martin M et al (2011) Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study. Ann Oncol Martin M et al (2011) Pegylated liposomal doxorubicin in combination with cyclophosphamide and trastuzumab in HER2-positive metastatic breast cancer patients: efficacy and cardiac safety from the GEICAM/2004-05 study. Ann Oncol
29.
go back to reference Joensuu H et al (2011) Very high quantitative tumor HER2 content and outcome in early breast cancer. Ann Oncol Joensuu H et al (2011) Very high quantitative tumor HER2 content and outcome in early breast cancer. Ann Oncol
31.
go back to reference Guarneri V et al (2006) Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol 24(25):4107–4115PubMedCrossRef Guarneri V et al (2006) Long-term cardiac tolerability of trastuzumab in metastatic breast cancer: the M.D. Anderson Cancer Center experience. J Clin Oncol 24(25):4107–4115PubMedCrossRef
32.
go back to reference Swedberg K et al (2008) Successful treatment of heart failure with devices requires collaboration. Eur J Heart Fail 10(12):1229–1235PubMedCrossRef Swedberg K et al (2008) Successful treatment of heart failure with devices requires collaboration. Eur J Heart Fail 10(12):1229–1235PubMedCrossRef
33.
go back to reference Seidman A et al (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20(5):1215–1221PubMedCrossRef Seidman A et al (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20(5):1215–1221PubMedCrossRef
Metadata
Title
Heart to heart with trastuzumab: a review on cardiac toxicity
Author
Serena Di Cosimo
Publication date
01-12-2011
Publisher
Springer-Verlag
Published in
Targeted Oncology / Issue 4/2011
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-011-0203-8

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