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Influence of Tamoxifen and Estradiol on the Growth of Human Breast Cancer Cells in Vitro¹

Departments of Medicine [B. M. A., P. G., O. H. P.] and Mathematics and Statistics [N. H. G.], Case Western Reserve University, Cleveland, Ohio 44106

Cells obtained from freshly resected human breast cancer were grown in vitro utilizing the soft agar technique. The effects of adding an antiestrogen (tamoxifen, TAM) and 17ß-estradiol alone or simultaneously on cell growth were assessed. The addition of TAM (10^-6 M) to the medium resulted in a significant decrease in cell growth in 26 of 36 (72%) estrogen receptor (ER)-positive tumors and in one of 5 ER-negative tumors (20%). The degree of inhibition caused by TAM was significantly higher in the ER-positive tumors that also contain the progesterone receptor (PgR) as compared to those that lacked that receptor (i.e., PgR negative) (46.2 ± 2% versus 36.2 ± 1.2% inhibition, P < 0.01). The simultaneous addition of 17ß-estradiol (10^-8 M) neutralized the inhibitory effect of TAM (10^-6 M) in the majority of tumors. With the presence of serum in the medium, the addition of 17ß-estradiol alone resulted in an enhancement of cell growth in 6 of 17 tumors. However, because of the confounding effects of serum in the medium, we studied the individual effect of 17ß-estradiol (10^-8 M) when added alone under serum-free conditions. Of 20 tumors studied, 17ß-estradiol significantly enhanced cell growth in 12. There was a 67.8 ± 12.6% increase in the number of colonies formed in these 12 responding tumors. One of these 12 responding tumors was ER negative as well as PgR negative, while the rest were all ER positive. These in vitro studies demonstrate that this approach can provide valuable information on endocrine mechanisms controlling the growth of human breast cancer.

¹ Supported in part by grants from the Cleveland Foundation and the Hugoton Foundation.

Received 8/ 9/85. Revised 2/20/86. Accepted 3/ 7/86.