Serum HER-2/neu and response to the aromatase inhibitor letrozole versus tamoxifen

被引:95
作者
Lipton, A
Ali, SM
Leitzel, K
Demers, L
Harvey, HA
Chaudri-Ross, HA
Brady, C
Wyld, P
Carney, W
机构
[1] Penn State Univ, Milton S Hershey Med Ctr, Dept Med, Div Hematol Oncol HO46, Hershey, PA 17033 USA
[2] Vet Affairs Med Ctr, Lebanon, PA USA
[3] Novartis Pharmaceut Corp, E Hanover, NJ USA
[4] Bayer Corp, Tarrytown, NY USA
[5] Novartis Pharma AG, Basel, Switzerland
关键词
D O I
10.1200/JCO.2003.09.098
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: To determine the effect of elevated serum HER2/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 UP 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. (C) 2003 by American Society of Clinical Oncology.
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页码:1967 / 1972
页数:6
相关论文
共 22 条
[1]  
BENZ CC, 1993, BREAST CANCER RES TR, V24, P85
[2]   Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation [J].
Bunone, G ;
Briand, PA ;
Miksicek, RJ ;
Picard, D .
EMBO JOURNAL, 1996, 15 (09) :2174-2183
[3]  
CARNEY W P, 1991, Journal of Tumor Marker Oncology, V6, P53
[4]  
CLARK GM, 1991, CANCER RES, V51, P944
[5]  
COLOMER R, 1992, Proceedings of the American Association for Cancer Research Annual Meeting, V33, P82
[6]   Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-positive, estrogen receptor-positive primary breast cancer:: Evidence from a phase III randomized trial [J].
Ellis, MJ ;
Coop, A ;
Singh, B ;
Mauriac, L ;
Llombert-Cussac, A ;
Jänicke, F ;
Miller, WR ;
Evans, DB ;
Dugan, M ;
Brady, C ;
Quebe-Fehling, E ;
Borgs, M .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (18) :3808-3816
[7]   ACTIVATION OF THE ESTROGEN-RECEPTOR THROUGH PHOSPHORYLATION BY MITOGEN-ACTIVATED PROTEIN-KINASE [J].
KATO, S ;
ENDOH, H ;
MASUHIRO, Y ;
KITAMOTO, T ;
UCHIYAMA, S ;
SASAKI, H ;
MASUSHIGE, S ;
GOTOH, Y ;
NISHIDA, E ;
KAWASHIMA, H ;
METZGER, D ;
CHAMBON, P .
SCIENCE, 1995, 270 (5241) :1491-1494
[8]  
LANGTON BC, 1991, CANCER RES, V51, P2593
[9]   Elevated serum HER-2/neu level predicts decreased response to hormone therapy in metastatic breast cancer [J].
Lipton, A ;
Ali, SM ;
Leitzel, K ;
Demers, L ;
Chinchilli, V ;
Engle, L ;
Harvey, HA ;
Brady, C ;
Nalin, CM ;
Dugan, M ;
Carney, W ;
Allard, J .
JOURNAL OF CLINICAL ONCOLOGY, 2002, 20 (06) :1467-1472
[10]   MCF-7 BREAST-CANCER CELLS OVEREXPRESSING TRANSFECTED C-ERBB-2 HAVE AN IN-VITRO GROWTH ADVANTAGE IN ESTROGEN-DEPLETED CONDITIONS AND REDUCED ESTROGEN-DEPENDENCE AND TAMOXIFEN-SENSITIVITY IN-VIVO [J].
LIU, YL ;
ELASHRY, D ;
CHEN, D ;
DING, IYF ;
KERN, FG .
BREAST CANCER RESEARCH AND TREATMENT, 1995, 34 (02) :97-117