IMPAKT: Gene expression response to tamoxifen and breast cancer prognosis

May 12, 2010

Changes in gene expression levels in the early days after beginning tamoxifen (Nolvadex®) therapy may predict breast cancer prognosis, according to research presented at the IMPAKT Breast Cancer Conference in Brussels, Belgium.  Researchers assessed gene expression changes using an estrogen receptor-positive (ER+) mouse xenograft model of breast cancer.  On Days 2, 4, and 7 after initiating tamoxifen, they observed changes in the gene expression levels of genes such as BUB1B, CCNA2, CDKN3, MIKI67, and UBE2C which are involved in regulating cell cycle and cell proliferation.  But looking at the changes on Day 1 after the start of tamoxifen was too early and on Day 14 was too late. 

Human breast cancer cell lines showed similar gene expression patterns with tamoxifen treatment compared with controls in two ER+ lines but not in an ER-negative line.  In four data sets representing 404 tamoxifen-treated ER+ breast cancer patients, gene expression level changes were significantly correlated with survival.  From a short period of neoadjuvant or adjuvant endocrine therapy, gene expression microarray testing results may identify women who do not show an early response from tamoxifen.  These are early results and more studies are needed to validate the biomarkers used in this study before using them in clinics to monitor tamoxifen efficacy.