fosfestrol and Breast-Neoplasms

A woman more than 5 years postmenopausal with right advanced breast cancer (T4, T3, M1, stage IV) was treated with a mild chemo-endocrine therapy. The regimen consisted of diethylstilbestrol diphosphate (Honvan) at 15 mg/day orally and cyclophosphamide at 100 mg/day orally. By the sixth month after administration, both the right breast cancer and multiple lymph node metastases completely disappeared. The change of hormonal therapy from Honvan, as estrogen, to tamoxifen, as antiestrogen, was done 2 years and 9 months after the beginning of initial treatment. The breast cancer recurred 9 months after the change of treatment. At that time, Honvan was again administered instead of tamoxifen. Complete remission was again obtained for 6 months beginning 2 months after the change of drugs, but then the tumor recurred. Although combination chemotherapy was undertaken, the patient died 5 years after initial treatment. These results suggest that chemoendocrine therapy using a low dose of Honvan and cyclophosphamide is effective for advanced breast carcinoma.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cyclophosphamide; Diethylstilbestrol; Female; Humans; Lymphatic Metastasis; Remission Induction; Tamoxifen

Diethylstilbestrol (DES), diethylstilbestrol monophosphate (DES-MP) and diethylstilbestrol diphosphate (DES-DP) were tested for their estrogen receptor affinity, estrogenic potency and mammary tumor-inhibiting activity in vitro and in vivo. DES had a much higher receptor binding affinity than its mono- or diphosphate. All three compounds inhibited the growth of the hormone-dependent MCF-7 and hormone-independent MDA-MB 231 breast cancer line only at relatively high concentrations. The estrogenic potency in the immature mouse uterine weight test decreased in the order DES greater than DES-MP much greater than DES-DP. The hormone-dependent MXT mammary tumor of the mouse was inhibited by all three compounds at a dosage of 1.0 mg/kg per week. At a dose of 0.01 mg/kg, DES, DES-MP, and DES-DP stimulated the tumor growth. Thus, for the first time, a biphasic effect on tumor growth was demonstrated in intact mature animals. As the effects of all three compounds were similar in this assay, a cleavage of the phosphate groups is likely. A decrease in estrogenic potency concomitant with a retained antitumor effect of DES-MP and DES-DP compared to DES was not demonstrable in the mature mouse using the MXT assay, only in the uterotrophic test in the immature mouse.

Topics: Animals; Breast Neoplasms; Cell Line; Diethylstilbestrol; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Estradiol; Female; Humans; In Vitro Techniques; Mammary Neoplasms, Experimental; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Receptors, Estradiol; Uterus

A 47-year-old man was admitted because of a left axillary tumor. A biopsy of the tumor disclosed adenocarcinoma. The bone survey showed multiple sclerotic metastases. Thirteen months after his first admission, a left breast tumor developed and a simple mastectomy revealed a papillotubular carcinoma. Skin metastases appeared postoperatively and were exacerbated with accumulation of pericardial effusion and a high CEA level (401.7 ng/ml) despite radiation and chemotherapy. Estrogen therapy with diethylstilbestrol sodium phosphate was started, resulting in the disappearance of pericardial effusion and skin metastases. The patient remains well 10 months after starting estrogen therapy with a normal CEA level.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Agents; Breast Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Drug Administration Schedule; Fluorouracil; Humans; Male; Middle Aged; Tegafur