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 treating a breast cancer patient, who has been previously treated with a first anticancer agent and has cancer cells that are estrogen receptor alpha negative, the method comprising administering to the patient a therapeutically effective amount of a combination of a second anticancer agent and a glucocorticoid receptor antagonist (GRA) wherein the breast cancer patients were previously treated with the first anticancer agent more than two weeks prior to the combination.
2. The method of claim 1 wherein the first anticancer agent is an aromatase inhibitor.
3. The method of claim 1 wherein the first anticancer agent is a chemotherapeutic.
4. The method of claim 3 wherein the breast cancer cells are resistant to the first chemotherapeutic agent.
5. The method of claim 1 wherein the second anticancer agent is a chemotherapeutic.
6. The method of claim 1 wherein the second anticancer agent is an aromatase inhibitor or tamoxifen.
7. The method of claim 1 wherein the second anticancer agent is a platinum based agent, a nucleoside analog, or microtubule formation inhibitor.
8. The method of claim 1 wherein the second anticancer agent is selected from the group consisting of gemcitabine, carboplatin, cisplatin or eribulin.
9. The method of claim 1 wherein the second anticancer agent is selected from the group consisting of a serine/threonine kinase inhibitor, a tyrosine kinase inhibitor, an angiogenesis inhibitor; and, an anti-epidermal growth factor receptor antibody.
10. The method of claim 1 wherein the second anticancer agent is a taxane or a camptothecin.
11. The method of claim 1 wherein the first and second anticancer agents are the same.
12. The method of claim 1 wherein the first and second anticancer agents are different.
13. The method of claim 1 wherein the second anticancer agent is radiation.
14. The method of claim 1 wherein the second anticancer agent is an antibody.
15. The method of claim 14 wherein the antibody is an anti-epidermal growth factor receptor antibody.
16. The method of claim 14 wherein the GRA is an aryl pyrazolo azadecalin.
17. The method of claim 1 wherein the cancer patient is treated with a GRA and a second anticancer agent that is a combination of a second chemotherapeutic agent and either an immunotherapeutic or radiation therapy or both.
18. The method of claim 1 wherein the GRA is in a class of compounds selected from the group consisting of octahydrophenanthrenes, pyrimidinediones, dihydropyridines, dihydroisoquinolines and azadecalins.
19. The method of claim 1 wherein the GRA is in the class of azadecalin compounds.
20. The method of claim 1 , wherein the glucocorticoid receptor antagonist is administered to the patient before the second anticancer agent.
21. The method of claim 1 , wherein the glucocorticoid receptor antagonist is administered to the patient after the second anticancer agent.
22. The method of claim 1 , wherein the glucocorticoid receptor antagonist and the second anticancer agent are administered to the patient at the same time.
23. The method of claim 1 , wherein the glucocorticoid receptor antagonist is administered prior to and after administration of the second chemotherapeutic.
24. The method of claim 1 where the patient is treated with radiation therapy after administration of the glucocorticoid receptor antagonist.
25. The method of claim 1 wherein the cancer cells are PR − .
26. The method of claim 1 wherein the cancer cells are HER2 − .
27. The method of claim 1 wherein the cancer cells are both PR − and HER2 − .
28. The method of claim 1 wherein the breast cancer cells do not express estrogen receptor alpha at a level detectable by immunohistochemistry.
29. The method of claim 1 wherein the therapeutically effective amount reduces the number of breast cancer cells in the patient.
30. The method of claim 1 wherein the therapeutically effective amount inhibits the growth of existing breast cancer cells.