title: Response and cardiac toxicity of trastuzumab given in conjunction with weekly paclitaxel after doxorubicin/cyclophosphamide.
abstract: BACKGROUND
  Adjuvant trastuzumab improves relapse-free survival in HER2-overexpressing breast cancer but is associated with cardiac toxicity. This phase II study was undertaken to determine the neoadjuvant clinical and pathologic response rate and the acute and chronic cardiac toxicity of trastuzumab given with weekly paclitaxel after AC (doxorubicin/cyclophosphamide).
  
  
  METHODS
  Fifty-two women with newly diagnosed, stage II-IV, HER2-overexpressing breast cancer received AC for 4 cycles, followed by weekly TP (paclitaxel/trastuzumab) for 12 weeks, neoadjuvantly or adjuvantly, followed by 40 weeks of adjuvant trastuzumab.
  
  
  RESULTS
  Congestive heart failure occurred in 4% of patients (95% confidence interval [CI], 0.5%-13.2%). Asymptomatic left ventricular ejection fraction (LVEF) decreases to < 50% occurred in 21% of patients (95% CI, 11.1%-34.7%); all but 1 recovered by 1.5 years. Median LVEF decreased progressively during therapy from 65% before therapy (95% CI, 63%-66%) to 62% after AC (95% CI, 59%-64%) and 58% after AC-TP (95% CI, 56%-64%; P < 0.01 for each decrease). The decrease in LVEF persisted 1.5 years after study entry at 57% (95% CI, 54%-60%), although all but 1 of the most severe decreases to < 50% recovered to normal. Clinical response rate among 37 patients treated neoadjuvantly was 86%, and the pathologic complete response rate was 19% (95% CI, 8%-35.2%). Because of withdrawals for toxicity, refractory disease, and patient preference, only 35% of patients completed the entire regimen.
  
  
  CONCLUSIONS
  In this study, the AC-TP regimen resulted in a high clinical but moderate pathologic response rate, and although asymptomatic cardiac systolic dysfunction was common, most of the severe decreases recovered over time.
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, NC 27599-7305, USA.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kelly
authors.forename: Gretchen
authors.initials: G
authors.lastname: Kimmick
authors.forename: E Claire
authors.initials: EC
authors.lastname: Dees
authors.forename: Frances
authors.initials: F
authors.lastname: Collichio
authors.forename: Lisa
authors.initials: L
authors.lastname: Gatti
authors.forename: Lynda
authors.initials: L
authors.lastname: Sawyer
authors.forename: Anastasia
authors.initials: A
authors.lastname: Ivanova
authors.forename: Lynn
authors.initials: L
authors.lastname: Dressler
authors.forename: Mark L
authors.initials: ML
authors.lastname: Graham
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009657:North Carolina; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab