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Serum HER-2/neu and Response to the Aromatase Inhibitor Letrozole Versus Tamoxifen

From the Milton S. Hershey Medical Center, Hershey, PA; Veterans Affairs Medical Center, Lebanon, PA; Novartis Pharmaceutical Corporation, East Hanover, NJ; Bayer Corporation, Tarrytown, New York; and Novartis Pharma AG, Basel, Switzerland.

Address reprint requests to Allan Lipton, MD, Penn State Milton S. Hershey Medical Center, Department of Medicine, Division of Hematology/Oncology HO46, 500 University Dr, PO Box 850, Hershey, PA 17033; email: alipton{at}psu.edu.

Purpose: 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.

Patients and 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.

Conclusion: 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.

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