Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
BACKGROUND
Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy.


METHODS
This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy.


RESULTS
Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab.


CONCLUSIONS
One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. (ClinicalTrials.gov number, NCT00045032.)
Piccart-Gebhart
Martine J
MJ
Medicine Department, Jules Bordet Institute, Blvd. de Waterloo 125, 1000 Brussels, Belgium. martine.piccart@bordet.be
Procter
Marion
M
Leyland-Jones
Brian
B
Goldhirsch
Aron
A
Untch
Michael
M
Smith
Ian
I
Gianni
Luca
L
Baselga
Jose
J
Bell
Richard
R
Jackisch
Christian
C
Cameron
David
D
Dowsett
Mitch
M
Barrios
Carlos H
CH
Steger
Günther
G
Huang
Chiun-Shen
CS
Andersson
Michael
M
Inbar
Moshe
M
Lichinitser
Mikhail
M
Láng
István
I
Nitz
Ulrike
U
Iwata
Hiroji
H
Thomssen
Christoph
C
Lohrisch
Caroline
C
Suter
Thomas M
TM
Rüschoff
Josef
J
Suto
Tamás
T
Greatorex
Victoria
V
Ward
Carol
C
Straehle
Carolyn
C
McFadden
Eleanor
E
Dolci
M Stella
MS
Gelber
Richard D
RD
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012008:Recurrence; D016019:Survival Analysis; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab