Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.
BACKGROUND
Aromatase inhibitors are considered standard adjuvant endocrine treatment of postmenopausal women with hormone receptor-positive breast cancer, but it remains uncertain whether aromatase inhibitors should be given upfront or sequentially with tamoxifen. Awaiting results from ongoing randomized trials, we examined prognostic factors of an early relapse among patients in the BIG 1-98 trial to aid in treatment choices.


METHODS
Analyses included all 7707 eligible patients treated on BIG 1-98. The median follow-up was 2 years, and the primary end point was breast cancer relapse. Cox proportional hazards regression was used to identify prognostic factors.


RESULTS
Two hundred and eighty-five patients (3.7%) had an early relapse (3.1% on letrozole, 4.4% on tamoxifen). Predictive factors for early relapse were node positivity (P < 0.001), absence of both receptors being positive (P < 0.001), high tumor grade (P < 0.001), HER-2 overexpression/amplification (P < 0.001), large tumor size (P = 0.001), treatment with tamoxifen (P = 0.002), and vascular invasion (P = 0.02). There were no significant interactions between treatment and the covariates, though letrozole appeared to provide a greater than average reduction in the risk of early relapse in patients with many involved lymph nodes, large tumors, and vascular invasion present.


CONCLUSIONS
Upfront letrozole resulted in significantly fewer early relapses than tamoxifen, even after adjusting for significant prognostic factors.
Mauriac
L
L
French Breast Cancer Group, Institut Bergonié Bordeaux, France. mauriac@bergonie.org
Keshaviah
A
A
Debled
M
M
Mouridsen
H
H
Forbes
J F
JF
Thürlimann
B
B
Paridaens
R
R
Monnier
A
A
Láng
I
I
Wardley
A
A
Nogaret
J-M
JM
Gelber
R D
RD
Castiglione-Gertsch
M
M
Price
K N
KN
Coates
A S
AS
Smith
I
I
Viale
G
G
Rabaglio
M
M
Zabaznyi
N
N
Goldhirsch
A
A
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D009570:Nitriles / Q000008:administration & dosage; D017698:Postmenopause; D011379:Prognosis; D013629:Tamoxifen / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole