HER-2 EXPRESSION AND RESPONSE TO TAMOXIFEN IN ESTROGEN RECEPTOR-POSITIVE BREAST-CANCER - A SOUTHWEST-ONCOLOGY-GROUP STUDY

HER-2/neu is a growth factor receptor, the expression of which has bee n associated with a more aggressive breast tumor biology and resistanc e to some types of chemotherapy. Preliminary laboratory and clinical d ata have led to claims that HER-2/neu expression is also associated wi th resistance to tamoxifen, Therefore, to test the hypothesis that HER -2/neu expression is associated with a poorer response to tamoxifen, a shorter time to treatment failure (TTF), and worse survival in estrog en receptor (ER)-positive metastatic breast cancer, we examined 205 pa raffin-embedded blocks of tumors from patients enrolled on Southwest O ncology Group 8228 for HER-2/neu expression, Tumors were ER positive ( ER level >3 fmol/mg cytosolic protein in either primary tumors or meta stases), and patients had not received any prior therapy for metastati c disease. All patients were treated with daily tamoxifen, The study b egan in 1982, and median follow-up of patients who are still alive is now 9 years, Membrane staining for HER-2/neu was evaluated by immunohi stochemistry using antibody TAB 250 and was scored according to the pr oportion of cells staining positive; tumors were deemed positive if >1 % of the cells stained for HER-2/neu, HER-2/neu positivity was associa ted with lower ER values (P = 0.04) and low bcl-2 (P = 0.01), HER-2/ne u positivity was not significantly associated with response rate (nega tive versus positive, 57 versus 54%; P = 0.67), TTF (median, 8 versus 6 months; P = 0.15), or survival (median, 31 versus 29 months; P = 0.3 6), There was also no significant evidence of a progressive relationsh ip between :ln increasing proportion of cells expressing HER-2/neu and a shorter TTF or survival, HER-2/neu expression in ER-positive metast atic breast cancer is not significantly associated with a poorer respo nse to tamoxifen or a more aggressive clinical course, Earlier suggest ions to the contrary may have been due to failure to rigorously exclud e ER-negative tumors, which are much less likely to respond to tamoxif en and more likely to have high HER-2/neu levels.