TAMOXIFEN STIMULATES IN-VIVO GROWTH OF DRUG-RESISTANT ESTROGEN RECEPTOR-NEGATIVE BREAST-CANCER

An estrogen receptor-negative, multidrug-resistant MDA-MB-A1 human bre ast cancer cell line was growth in culture with and without a noninhib itory concentration (0.5 muM) of tamoxifen for 122 days. Tamoxifen-tre ated and control cells were inoculated into opposite flanks of nine nu de mice, where they produced measurable tumors in every case. Six of t he animals were treated with tamoxifen at 500 mug/day for 22 days. Alt hough no inhibitory nor stimulatory effect of tamoxifen was seen in vi tro, tamoxifen had a clear tumor-growth-stimulating effect in mice. Th e most pronounced stimulatory effects were observed in the cells that had been cultured with tamoxifen. Within 3 weeks of the start of tamox ifen therapy, the cells grown in the presence of tamoxifen produced tu mors with a mean size of 380 mm2, whereas the cells not pretreated wit h tamoxifen had tumors of 220 mm2. In contrast, in mice not receiving tamoxifen, the sizes of the tumors were 190 and 140 mm2, respectively. These preliminary results suggest that prolonged in vitro tamoxifen e xposure induces cellular changes that result in tumors that are stimul ated to grow faster in mice following tamoxifen treatment.