title: Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human epidermal growth factor receptor 2-positive breast cancer.
abstract: OBJECTIVE
  Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care.
  
  
  METHODS
  In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified.
  
  
  RESULTS
  At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab.
  
  
  CONCLUSIONS
  The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/ cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project, East Commons Professional Building, Four Allegheny Center, 5th Floor, Pittsburgh, PA 15212, USA.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Romond
authors.forename: Jong-Hyeon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Priya
authors.initials: P
authors.lastname: Rastogi
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
authors.forename: Charles E
authors.initials: CE
authors.lastname: Geyer
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ewer
authors.forename: Vikas
authors.initials: V
authors.lastname: Rathi
authors.forename: Louis
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: Adam
authors.initials: A
authors.lastname: Brufsky
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Azar
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: John L
authors.initials: JL
authors.lastname: Zapas
authors.forename: Jonathan
authors.initials: J
authors.lastname: Polikoff
authors.forename: Howard M
authors.initials: HM
authors.lastname: Gross
authors.forename: David D
authors.initials: DD
authors.lastname: Biggs
authors.forename: James N
authors.initials: JN
authors.lastname: Atkins
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tan-Chiu
authors.forename: Ping
authors.initials: P
authors.lastname: Zheng
authors.forename: Greg
authors.initials: G
authors.lastname: Yothers
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000139:chemically induced* / Q000188:drug therapy; D006334:Heart Function Tests; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015233:Models, Statistical; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D003520:Cyclophosphamide; D066246:ErbB Receptors; D000068878:Trastuzumab; D017239:Paclitaxel