neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.
OBJECTIVE
It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN.


METHODS
A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors.


RESULTS
Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients.


CONCLUSIONS
neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.
Andrulis
I L
IL
Samuel Lunenfeld Research Institute, Department of Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada. andrulis@mshri.on.ca
Bull
S B
SB
Blackstein
M E
ME
Sutherland
D
D
Mak
C
C
Sidlofsky
S
S
Pritzker
K P
KP
Hartwick
R W
RW
Hanna
W
W
Lickley
L
L
Wilkinson
R
R
Qizilbash
A
A
Ambus
U
U
Lipa
M
M
Weizel
H
H
Katz
A
A
Baida
M
M
Mariz
S
S
Stoik
G
G
Dacamara
P
P
Strongitharm
D
D
Geddie
W
W
McCready
D
D
D001365:Axilla; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D016019:Survival Analysis