Methods and compositions related to glucocorticoid receptor antagonists and breast cancer
Embodiments of the invention are directed to methods of determining the prognosis of a breast cancer patient by evaluating the activity of the glucocorticoid receptor in tumor cells. Other embodiment include methods of treating breast cancer cells, particularly, chemo-resistant cells, with a glucocorticoid receptor antagonist and an anticancer agent or compound.
1. A method of killing breast cancer cells comprising administering to a breast cancer patient an effective amount of a combination of anti-cancer compounds, wherein the breast cancer cells do not express detectable levels of estrogen receptor alpha, and wherein the anticancer compounds comprise a glucocorticoid receptor antagonist and a chemotherapeutic.
2. The method of claim 1 , wherein the breast cancer cells were previously administered a first chemotherapeutic more than two weeks prior to the combination of anti-cancer compounds.
3. The method of claim 2 , wherein the breast cancer cells that were previously administered a first chemotherapeutic are chemo-resistant.
4. The method of claim 3 , wherein the breast cancer cells are determined not to be chemo-sensitive or are determined to be chemo-resistant.
5. The method of claim 1 , wherein the breast cancer cells are glucocorticoid receptor-positive (GR+).
6. The method of claim 1 , wherein the patient is determined to have breast cancer cells that are GR+.
7. The method of claim 1 , wherein the combination of anti-cancer compounds is administered within 1 week of each anti-cancer compound.
8. The method of claim 7 , wherein the combination of anti-cancer compounds is administered within 24 hours of each anti-cancer compound.
9. The method of claim 7 , wherein the glucocorticoid receptor antagonist is administered prior to the chemotherapeutic.
10. The method of claim 9 , wherein the glucocorticoid receptor antagonist is administered up to three days prior to administering the chemotherapeutic.
11. The method of claim 7 , wherein the glucocorticoid receptor antagonist is administered after the chemotherapeutic is administered.
12. The method of claim 9 , wherein the glucocorticoid receptor antagonist is also administered after the chemotherapeutic is administered.
13. The method of claim 1 , wherein the glucocorticoid receptor antagonist is administered prior to and after administration of the chemotherapeutic.
14. The method of claim 13 , wherein the glucocorticoid receptor antagonist is administered up to three days prior to administration of the chemotherapeutic.
15. The method of claim 1 , wherein the glucocorticoid receptor antagonist has undetectable or a lower level of activity as a progesterone receptor antagonist.
16. The method of claim 15 , wherein the glucocorticoid receptor antagonist does not have detectable progesterone receptor antagonist activity.
17. The method of claim 1 , wherein the breast cancer is an unresectable breast cancer.
18. The method of claim 1 , wherein dexamethasone has not been administered to the patient within 24 hours of administration of the glucocorticoid receptor antagonist.
19. The method of claim 1 , wherein the breast cancer cells were previously administered a first apoptosis inducing agent more than two weeks prior to the glucocorticoid receptor antagonist.
20. The method of claim 19 , wherein at least one apoptosis inducing agent is radiation, a chemotherapeutic, or an immunotherapy.