Predictive value of SRC-1 for tamoxifen response of recurrent breast cancer

Tamoxifen causes an objective response in about one-third of metastatic breast cancer and in only half of the breast cancer patients with estrogen receptor (ER) positive tumors. Steroid-receptor coactivator-1 (SRC-1) appears to be a general coactivator for steroid receptors and rate limiting factor necessary for efficient ER transactivation. We aimed to evaluate whether SRC-1 expression is an additional factor for prediction of response to first-line tamoxifen therapy in patients who developed recurrent disease. Here for the first time, we report on SRC-1 expression using a semi-quantitative RT-PCR in 21 primary breast tumors, seven mammary tumor cell-lines, 12 fibroblast cultures, and six normal breast tissues. The highest levels of SRC-1 were observed in normal tissues, intermediate levels in tumor tissues, and the lowest levels in breast tumor cell-lines. There was no relationship between the levels of SRC-1 in these primary tumors and the proportion of tumor cells within the surgical samples, nor with ER status. The median SRC-1 level was, however, lower in tumors from patients that did not respond to tamoxifen. Our findings suggest that high levels of SRC-1 indicate a favorable response to tamoxifen of patients with recurrent breast cancer. Abbreviations: PgR, progesterone receptor; ER, estrogen receptor; GR, glucocorticoid receptor; TR, thyroid hormone receptor; RXR, retinoid X receptor; SRC-1, steroid-receptor coactivator-1; EGF, epidermal growth factor; TGF, transforming growth factor; IGF, insulin like growth factor; UPA, urokinase-type plasminogen activator