TY - JOUR
T1 - 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
T2 - NSABP B-31
AU - Tan-Chiu, Elizabeth
AU - Yothers, Greg
AU - Romond, Edward
AU - Geyer, Charles E.
AU - Ewer, Michael
AU - Keefe, Deborah
AU - Shannon, Richard P.
AU - Swain, Sandra M.
AU - Brown, Ann
AU - Fehrenbacher, Louis
AU - Vogel, Victor G.
AU - Seay, Thomas E.
AU - Rastogi, Priya
AU - Mamounas, Eleftherios P.
AU - Wolmark, Norman
AU - Bryant, John
PY - 2005
Y1 - 2005
N2 - 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. 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. 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 ≥ 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. 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.
AB - 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. 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. 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 ≥ 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. 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.
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U2 - 10.1200/JCO.2005.02.4091
DO - 10.1200/JCO.2005.02.4091
M3 - Article
C2 - 16258083
AN - SCOPUS:29744442709
VL - 23
SP - 7811
EP - 7819
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 31
ER -