| Abstract: | The effect of clomiphene citrate given in vivo upon the in vitro uptake of labeled estradiol (tritiated-E2) was investigated in a 60-year-old patient with breast cancer who had had a mastectomy 10 months earlier followed by radiotherapy. Multiple subcutaneous metastatic nodules and enlargement of the liver were present but bone metastases could not be shown. A biopsy from a subcutaneous nodule, taken prior to present treatment, showed 86 fmol estradiol binding sites per mg of cytoplasmic protein with a dissociation constant of the estradiol-estradiol binding protein interaction of 2.8 X 10 -10 M. The patient was treated with 200 mg clomiphene citrate daily. Subjective symptoms improved and a reduction of skin nodule size and of liver enlargement followed. The serum enzymes alkaline phosphatase, nucleotidase, and phosphohexoseisomerase were diminished. A 2nd biopsy taken at Day 26 of treatment with clomiphene citrate showed complete inhibition of labeled estradiol tritiated-E2 uptake by the cytosol protein. This finding is thought to show the absence of free binding sites after clomiphene citrate therapy. Microscopic studies of biopsy material were unchanged. These results are thought to be the first to record human in vivo inhibition of trititated-E2 uptake for EBP by an antiestrogen compound, although similar in vitro observations have been made in human tumor specimens. There is thought to be a potential value of antiestrogenic agents, alone or with inhibitors of prolactin secretion, to replace endocrine ablations and to predict the response to endocrine therapy. |
