Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial.
OBJECTIVE
The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy.


METHODS
The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2-positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF > or = 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction.


RESULTS
Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m(2) v 257 mg/m(2)) or epirubicin (480 mg/m(2) v 422 mg/m(2)) and had a lower screening LVEF and a higher body mass index.


CONCLUSIONS
Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.
Suter
Thomas M
TM
Swiss Cardiovascular Center, University Hospital Bern, Inselspital, Bern, Switzerland. thomas.suter@insel.ch
Procter
Marion
M
van Veldhuisen
Dirk J
DJ
Muscholl
Michael
M
Bergh
Jonas
J
Carlomagno
Chiara
C
Perren
Timothy
T
Passalacqua
Rodolfo
R
Bighin
Claudia
C
Klijn
Jan G M
JG
Ageev
Fail T
FT
Hitre
Erika
E
Groetz
Juergen
J
Iwata
Hiroji
H
Knap
Malgorzata
M
Gnant
Michael
M
Muehlbauer
Susanne
S
Spence
Alison
A
Gelber
Richard D
RD
Piccart-Gebhart
Martine J
MJ
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab