epitiostanol and Breast-Neoplasms

Additive endocrine therapy of breast cancer was first initiated by androgen treatment through intramuscular administration which proved to be effective in about 25% of trial cases. It was followed by another trial of massive administration of estrogens mainly to patients of more than 60 years of age, and this showed a similar efficacy. Under these circumstances, additive endocrine therapy's position was established as a special therapy for advanced breast cancer. Breast cancer patients have a considerably longer period of progress after disease recurrence than in other types of cancer, so oral androgens were developed for treating recurrent breast cancer patients at home. However, the side effects of androgens (e.g., virilization, hepatic disorders) presented problems with Long-term administration. Since then more androgens with less side effects have been developed which have contributed to the remarkable progress of androgen therapy. On the other hand, recently an anti-estrogen was found which specifically antagonizes estrogen and has few side effects. Additive endocrine therapy's reputation has improved with the emergence of this anti-estrogen agent. Another study has also been started on a progesterone agent which is completely different from conventional sex hormone agents. Anti-estrogen agent is widely accepted for post-operative adjuvant endocrine therapy of breast cancer taking over as the conventional post-operative adjuvant chemotherapy, and also as a partner of chemo-endocrine therapy.

Topics: Androstanols; Breast Neoplasms; Castration; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Double-Blind Method; Female; Fluoxymesterone; Humans; Lymphatic Metastasis; Mastectomy; Menopause; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Testosterone

A patient with stage IV advanced breast cancer with multiple metastasis (bones of the whole body, lungs) were treated by ovariectomy, administration of an non-steroidal antiestrogen (tamoxifen) and mild chemotherapeutic drugs, with favorable results. After four years, however, the patient had a relapse of the cancer. A steroidal antiestrogen (epitiostanol) was then administered with satisfactory results. When a breast cancer relapse occurs in patients once treated successfully with endocrinotherapy, a different form of endocrinotherapy should be tried. There is a possibility that the mechanism of action of Epitiostanol, which is regarded as a steroidal antiestrogen, is different from that of tamoxifen in which an estrogen receptor (ER) system is included.

Topics: Androstanols; Breast Neoplasms; Combined Modality Therapy; Drug Therapy, Combination; Estrogen Antagonists; Female; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Ovariectomy; Tamoxifen

We have recently isolated retinoic acid-resistant clones U-2 and U-3 from human breast cancer cell line MCF-7 (Ueda et al. (1985) Cancer Res. 45, 3332-3338). Growth of MCF-7 cells was found to be stimulated by estradiol but that of U-2 or U-3 was not. Cytosol from U-2 or U-3 cells contained no detectable estradiol receptor activity, whereas that from the parental MCF-7 cells showed estradiol receptor activity of 32 fmol/mg cytosol protein with a Kd of 2.6 X 10(-10) M by Scatchard analysis. Sucrose gradient centrifugation analysis of the cytosol fraction confirmed the presence of estradiol receptor activity in MCF-7 but not in U-2. Cytosol from MCF-7 and U-2 cells showed progesterone receptor activities of 106 fmol/mg protein with a Kd of 7.4 X 10(-10) M and 13 fmol/mg protein with a Kd of 9.9 X 10(-10) M, respectively. Addition of estradiol to the culture medium of the cells increased the level of progesterone receptor about 2-fold in MCF-7, but not in U-2. U-2 or U-3 cells showed about 5-fold higher resistance to an antiestrogen, tamoxifen, than MCF-7, and they were also 300- to 1,000-fold more resistant to other antiestrogens, epitiostanol and medroxyprogesterone, than MCF-7. The altered cellular sensitivity of U-2 or U-3 to the hormone antagonists is discussed in relation to the absence or presence of hormone receptors.

Topics: Androstanols; Breast Neoplasms; Cell Division; Cell Line; Centrifugation, Density Gradient; Dose-Response Relationship, Drug; Estradiol; Female; Humans; Kinetics; Mutation; Promegestone; Receptors, Cell Surface; Receptors, Estradiol; Receptors, Progesterone; Tamoxifen

Topics: Adult; Androstanols; Antineoplastic Agents; Breast Neoplasms; Carcinoma; Female; Fluoxymesterone; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovariectomy; Tamoxifen