Treatment option for antiestrogen-resistant breast cancers, PR+ breast cancers and familial BRCA1 ca

Felixthecat Member Posts: 37
edited March 2014 in Breast Cancer #1
If all else fails and you are suitable candidate this drug can be obtained via the US FMF's Compassionate Use Program so please bear that in mind:

1998 - Additive effect of mifepristone and tamoxifen on apoptotic pathways in MCF-7 human breast cancer cells:
“Our data further suggest that a combination of an antiprogestin with tamoxifen may be more effective than tamoxifen monotherapy in the management of human breast cancer.”

2004: Mifepristone Induces Growth Arrest, Caspase Activation, and Apoptosis of Estrogen Receptor-Expressing, Antiestrogen-Resistant Breast Cancer Cells
• “We demonstrate that: (a) estrogen receptor+progesterone receptor+, 4-OHT-resistant clonal variants can be isolated from an MCF-7 cell line in the absence of antiestrogen selection; and (b) MIF and MIF plus 4-OHT combination therapy induces growth arrest and active cell death of the antiestrogen-resistant breast cancer cells. These preclinical findings show potential for a combined hormonal regimen of an antiestrogen and an antiprogestin to combat the emergence of antiestrogen-resistant breast cancer cells and, ultimately, improve the therapeutic index of antiestrogen therapy.”

2006: Prevention of Brca1-Mediated Mammary Tumorigenesis in Mice by a Progesterone Antagonist
• Women with mutations in the breast cancer susceptibility gene BRCA1 are predisposed to breast and ovarian cancers. Why the BRCA1 protein suppresses tumor development specifically in ovarian hormone–sensitive tissues remains unclear. We demonstrate that mammary glands of nulliparous Brca1/p53-deficient mice accumulate lateral branches and undergo extensive alveologenesis, a phenotype that occurs only during pregnancy in wild-type mice. Progesterone receptors, but not estrogen receptors, are overexpressed in the mutant mammary epithelial cells because of a defect in their degradation by the proteasome pathway. Treatment of Brca1/p53-deficient mice with the progesterone antagonist mifepristone (RU 486) prevented mammary tumorigenesis. These findings reveal a tissue-specific function for the BRCA1 protein and raise the possibility that antiprogesterone treatment may be useful for breast cancerpreventioninindividuals with BRCA1 mutations.
2003: Glucocorticoid Cotreatment Induces Apoptosis Resistance toward Cancer Therapy in Carcinomas1

• “....In conclusion, GCs are widely used in high doses in the therapy of leukemias and lymphomas and are also used as antiemetics or preservatives for normal cells during chemotherapy of solid tumors. In addition, GCs are among the most widely used anti-inflammatory drugs. In this study, we have shown that application of GCs renders certain tumors resistant or less susceptible to apoptosis after cancer therapy. This finding urges to carefully reconsider the widespread use of GCs in almost all treatment protocols for patients with solid cancers. In the clinical setting of cancer therapy, e.g., in antiemetic regimens, corticosteroids are usually given transiently to suppress acute side effects of cancer therapy. Although our experiments did not mimic precisely the clinical situation because we administered DEX daily to achieve steady-state levels, short-term exposure to DEX may nevertheless be sufficient to abrogate or diminish the efficacy of concomitant chemotherapy in cancer patients in vivo. This is suggested by our experiments where DEX was found to down-regulate basal and cisplatin-induced expression of apoptosis effectors within 24 h in vitro. Also, endogenous levels of GCs and those existing as a consequence of administered hormones may render solid tumors less susceptible to apoptosis after cancer therapy. The administration of steroid/receptor agonists such as RU486 might be beneficial before chemotherapy and radiotherapy to enhance cell death of solid tumor cells.