Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen.
OBJECTIVE
To determine the effect of elevated serum HER-2/neu on the response of metastatic breast cancer patients to an aromatase inhibitor versus an antiestrogen.


METHODS
Five hundred sixty-two estrogen receptor-positive metastatic breast cancer patients were randomized to first-line hormone therapy with either letrozole or tamoxifen. An automated enzyme-linked immunosorbent assay was used to detect serum HER-2/neu.


RESULTS
For patients with normal serum HER-2/neu (70.5%), objective response rate (ORR; 39% in letrozole-treated patients v 26% in tamoxifen-treated patients; P =.008), clinical benefit (CB; 57% v 45%; P =.016), time to progression (TTP; median, 12.2 v 8.5 months; P =.0019), and time to treatment failure (TTF; median, 11.6 v 6.2 months; P =.0066) were significantly better in patients treated with letrozole. In the elevated HER-2/neu group (29.5%), there was no significant difference in ORR (17% in letrozole-treated patients v 13% in tamoxifen-treated patients; P =.45) or CB (33% v 26%; P =.31), but there was a strong trend in favor of a longer TTP with letrozole (median, 6.1 v 3.3 months; P =.0596) and a significantly longer TTF with letrozole (median, 6.0 v 3.2 months; P =.0418). Multivariate analysis revealed that elevated serum HER-2/neu was a negative predictor for ORR and TTP.


CONCLUSIONS
Patients with normal serum HER-2/neu receiving letrozole demonstrated a significantly greater ORR and CB and longer TTP and TTF than patients receiving tamoxifen. Although in patients with elevated serum HER-2/neu there was no significant difference between letrozole and tamoxifen in ORR or CB, there was a strong trend favoring longer TTP and significantly longer TTF with letrozole.
Lipton
A
A
Penn State Milton S. Hershey Medical Center, Department of Medicine, Division of Hematology/Oncology HO46, 500 University Dr, PO Box 850, Hershey, PA 17033, USA. alipton@psu.edu
Ali
S M
SM
Leitzel
K
K
Demers
L
L
Harvey
H A
HA
Chaudri-Ross
H A
HA
Brady
C
C
Wyld
P
P
Carney
W
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009570:Nitriles / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D013557:Switzerland; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D014481:United States
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles