cortodoxone and Breast-Neoplasms

Megestrol acetate (MA) is of therapeutic value in breast cancer patients. This study was designed to evaluate the effects of different dosages of MA on endocrine events potentially influenced by the drug in relation to plasma level of MA and clinical effects in patients with advanced breast cancer. Eighteen postmenopausal patients were randomly distributed over six groups to receive daily 90, 180 or 270 mg of MA (niagestin) orally in a cross-over study consisting of 3 periods of 6 weeks. Complete remission was observed in 1 patient, partial remission in 9, no change in 4 and failure in 4 patients. During the 18 weeks of treatment plasma levels of MA gradually increased, irrespective of the dose administered. Significant rises of the basal and TRH-stimulated plasma PRL and basal insulin levels were observed, whereas LH and FSH, estradiol, SHBG and the pituitary-adrenal axis were suppressed. None of these metabolic effects showed a correlation with the clinical response. We concluded that treatment of metastatic breast cancer with 180 mg MA/day is effective and causes minimal adverse effects.

Topics: Administration, Oral; Aged; Blood Glucose; Breast Neoplasms; Cortodoxone; Drug Administration Schedule; Estradiol; Female; Humans; Insulin; Megestrol; Megestrol Acetate; Middle Aged; Neoplasm Metastasis; Pituitary Hormones, Anterior; Sex Hormone-Binding Globulin

The purpose of the study is to define AroER tri-screen's utility for identifying endocrine-disrupting chemicals (EDCs) that target aromatase and/or estrogen receptor (ER), and to measure the total estrogenic activity in biological specimens. ER-positive, aromatase-expressing MCF-7 breast cancer cells were stably transfected with an estrogen responsive element (ERE)-driven luciferase reporter plasmid to yield a new high-throughput screening platform-the AroER tri-screen. AroER tri-screen was capable of identifying estrogen precursors, such as cortodoxone, which function as estrogens through a two-step conversion process in aromatase-expressing tissue. Furthermore, the system proved useful for assessing EDC activity in biologically relevant samples. Estimating these activities is critical because natural estrogens and estrogenic EDCs are important factors in ER-positive breast cancer risk. As our research demonstrates, incorporating functionally active aromatase into the AroER tri-screen produces a powerful and unique tool to (1) identify new EDCs targeting aromatase and/or ER; (2) discover novel EDCs activated by aromatase; and (3) estimate overall estrogenic activities in biological samples as a potential intermediate risk factor for breast cancer.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cortodoxone; Drug Screening Assays, Antitumor; Endocrine Disruptors; Estrogens; Female; Gene Expression; Genes, Reporter; Humans; Receptors, Estrogen; Reproducibility of Results; Transfection