Changes in Estrogen Receptor, Progesterone Receptor, and pS2 Expression in Tamoxifen-resistant Human Breast Cancer

摘要: Changes in estrogen receptor (ER) expression and function may explain the development of tamoxifen resistance breast cancer. ER was measured by an immunohistochemical assay, validated for use tamoxifen-treated tumors against a biochemical enzyme immunoassay, 72 paired biopsies taken before treatment at progression or relapse on tamoxifen. Progesterone (PgR) pS2 gene were also immunohistochemically as indicator function. Overall frequency reduced from 37 (51%) pretamoxifen to 21 (29%) relapse, with significant reduction quantitative level (P < 0.0001; Wilcoxon signed rank sum test). Tumors treated primary that responded but then developed acquired frequently remained positive (ER+) relapse: 16 18 (89%) ER+ (75% these expressed either PgR pS2) 11 (61%) (82% continued express pS2). In contrast, only 3 20 (15%) progressed de novo pretamoxifen, all ER- progression. At progression, 6 (30%) high levels (mean H-score, 98) and/or (mean, 50% cells positive), despite being ER-. recurred during adjuvant therapy, including locoregional metastatic lesions, significantly 34 (53%) original tumor 10 = 0.002). likewise this group 0.001). This study confirms functional cancer is strong predictor response Although tamoxifen-resistant overall, associated maintained many tumors, whereas related lack expression. Recurrence ER/PgR-negative phenotype some tumors. These data imply separate mechanisms occur different clinical subgroups.