title: Long-term cardiac safety and outcomes of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab with and without lapatinib in patients with early breast cancer.
abstract: BACKGROUND
  The authors have previously reported 2 consecutive phase 2 trials in patients with early breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2 therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.2%, respectively.
  
  
  METHODS
  In trial A, patients received dd doxorubicin and cyclophosphamide (AC)→paclitaxel (T) (each given every 2 weeks) × 4 with trastuzumab (H) given × 1 year. In trial B, weekly T (weekly × 12) was substituted for ddT and lapatinib × 1 year was added. Herein, the authors report the longer-term incidence of CHF and distant disease-free survival (DDFS).
  
  
  RESULTS
  From January 2005 to May 2008, 165 patients enrolled (median age, 46 years, with a median left ventricular ejection fraction of 68% [range, 52%-81%]), 17%of whom had previous hypertension. With a median follow-up of 84 months (trial A) and 57 months (trial B), 1 additional patient developed CHF. Therefore, the cumulative incidence of CHF was 1.4% (95% confidence interval [95% CI], 1.36%-7.7%) for trial A and 4.2% (95% CI, 4.2%-10.4%) for trial B. The 5-year DDFS for trials A and B was 92% (95% CI, 83%-97%) and 89% (95% CI, 81%-94%), respectively.
  
  
  CONCLUSIONS
  Longer follow-up of these 2 studies has demonstrated that ddAC→TH only or with lapatinib is associated with a low risk of CHF and promising DDFS in patients with early breast cancer.
authors.affiliation: Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Morris
authors.forename: Neil M
authors.initials: NM
authors.lastname: Iyengar
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Carol
authors.initials: C
authors.lastname: Chen
authors.forename: Alyson
authors.initials: A
authors.lastname: Abbruzzi
authors.forename: Robert
authors.initials: R
authors.lastname: Lehman
authors.forename: Richard
authors.initials: R
authors.lastname: Steingart
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Oeffinger
authors.forename: Nancy
authors.initials: N
authors.lastname: Lin
authors.forename: Beverley
authors.initials: B
authors.lastname: Moy
authors.forename: Steven E
authors.initials: SE
authors.lastname: Come
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Hudis
authors.forename: Chau T
authors.initials: CT
authors.lastname: Dang
mesh_terms: 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; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003520:Cyclophosphamide; D004317:Doxorubicin; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: cardiac safety; dose-dense chemotherapy; early breast cancer; efficacy; lapatinib; trastuzumab