title: Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer.
abstract: OBJECTIVE
  Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer.
  
  
  OBJECTIVE
  To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer.
  
  
  METHODS
  In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years.
  
  
  METHODS
  Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year.
  
  
  METHODS
  Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported.
  
  
  RESULTS
  Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%.
  
  
  CONCLUSIONS
  Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, West Harrison, New York.
authors.forename: Chau
authors.initials: C
authors.lastname: Dang
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Julie
authors.initials: J
authors.lastname: Najita
authors.affiliation: Breast Cancer Research, Sarah Cannon Research Institute, Nashville, Tennessee.
authors.forename: Denise
authors.initials: D
authors.lastname: Yardley
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Kelly
authors.initials: K
authors.lastname: Marcom
authors.affiliation: Department of Medicine, Cardinal Bernardin Cancer Center, Loyola University Chicago, Chicago, Illinois.
authors.forename: Kathy
authors.initials: K
authors.lastname: Albain
authors.affiliation: Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco.
authors.forename: Hope
authors.initials: H
authors.lastname: Rugo
authors.affiliation: Department of Medicine, Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis.
authors.forename: Kathy
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellis
authors.affiliation: Department of Hematology Oncology, Hofstra North Shore-Long Island Jewish School of Medicine, Hempstead, New York.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Shapira
authors.affiliation: Department of Oncology, The Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Boston.
authors.forename: Beverly
authors.initials: B
authors.lastname: Moy
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: John
authors.initials: J
authors.lastname: Groarke
authors.affiliation: Department of Medicine, Cardio-Oncology Program, Vanderbilt School of Medicine, Nashville, Tennessee.
authors.forename: Javid
authors.initials: J
authors.lastname: Moslehi
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Ian
authors.initials: I
authors.lastname: Krop
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, West Harrison, New York.
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Tolaney
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects*; D013997:Time Factors; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D014481:United States; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human