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Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2005 Nov 01; Vol. 23 (31), pp. 7811-9. - Publication Year :
- 2005
-
Abstract
- Purpose: Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2) -positive breast cancer, but it increases frequency of cardiac dysfunction (CD) when used with or after anthracyclines.<br />Patients and Methods: National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms.<br />Results: Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients; 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for > or = 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity.<br />Conclusion: Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CD. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy.
- Subjects :
- Antibodies, Monoclonal, Humanized
Breast Neoplasms metabolism
Breast Neoplasms secondary
Chemotherapy, Adjuvant
Cyclophosphamide administration & dosage
Doxorubicin administration & dosage
Female
Heart Failure drug therapy
Humans
Incidence
Lymph Nodes
Lymphatic Metastasis
Middle Aged
Neoadjuvant Therapy
Paclitaxel administration & dosage
Trastuzumab
Ventricular Dysfunction, Left drug therapy
Antibodies, Monoclonal adverse effects
Antineoplastic Combined Chemotherapy Protocols adverse effects
Breast Neoplasms drug therapy
Heart drug effects
Heart Failure chemically induced
Receptor, ErbB-2 metabolism
Ventricular Dysfunction, Left chemically induced
Subjects
Details
- Language :
- English
- ISSN :
- 0732-183X
- Volume :
- 23
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 16258083
- Full Text :
- https://doi.org/10.1200/JCO.2005.02.4091