ANTAGONISM BETWEEN TAMOXIFEN AND DOXORUBICIN IN THE MCF-7 HUMAN BREAST-TUMOR CELL-LINE

Tamoxifen, an antiestrogen, and doxorubicin, an anthracycline antibiot ic, are each utilized alone and in combination in the treatment of bre ast carcinoma. In view of conflicting reports relating to the interact ion between these drugs, studies were undertaken to characterize the i nfluence of tamoxifen on growth inhibition by doxorubicin in the MCF-7 breast tumor cell line in vitro. Studies combining 5 mu M tamoxifen, a clinically relevant concentration, with various concentrations of do xorubicin, indicated that this drug combination produces antiprolifera tive effects that appear to be less than additive. Concentration-depen dent growth inhibition was analyzed further using various concentratio ns of tamoxifen and doxorubicin by the combination index-isobologram m ethod; this quantitative approach provided clear evidence of antagonis m between these agents, a finding with potential relevance to the trea tment of breast cancer.