Methods for the treatment of breast cancer

Abstract

Described herein are methods for the treatment of breast cancer in a subject. In particular, methods are provided for the treatment of resistant, metastatic breast cancer with a combination of entinostat and an aromatase inhibitor.

1 - 58 . (canceled) 
     
     
         59 . A method of selecting a patient for further entinostat-exemestane combination therapy comprising comparing the protein lysine acetylation level in a tissue sample obtained about 15 days after initiating therapy to the protein lysine acetylation levels determined prior to initiating therapy, wherein an increase in protein lysine acetylation level determined about 15 days after initiating therapy indicates the patient will benefit from further therapy. 
     
     
         60 . The method of  claim 59 , wherein determining the change in protein lysine acetylation level during the course of said therapy occurs after about 2 days of therapy, about 5 days of therapy, about 7 days of therapy, about 15 days of therapy, or about 21 days of therapy. 
     
     
         61 . The method of  claim 59 , wherein the protein lysine acetylation levels are obtained from a tissue sample selected from B-cells, T-cells, or monocytes. 
     
     
         62 . The method of  claim 59 , wherein the exemestane is administered daily. 
     
     
         63 . The method of  claim 59 , wherein entinostat is administered every 7 days of a 28-day cycle. 
     
     
         64 . The method of  claim 59 , wherein the entinostat-exemestane combination therapy comprises oral administration of entinostat every 7 days of a 28-day cycle, and oral administration of exemestane every day. 
     
     
         65 . The method of  claim 59 , wherein the step of determining the protein lysine acetylation level during the course of therapy is performed more than once. 
     
     
         66 . The method of  claim 59 , wherein the step of determining the protein lysine acetylation level during the course of therapy is performed once. 
     
     
         67 . The method of  claim 59 , further comprising selecting the patient for further treatment if the level of protein lysine acetylation level increases during the first and second week of the course of therapy. 
     
     
         68 . The method of  claim 59  wherein the protein lysine acetylation level in a tissue sample obtained after initiating therapy is determined more than once. 
     
     
         69 . The method of  claim 59  wherein the protein lysine acetylation level after initiating therapy is determined on days 2, 8 and 15. 
     
     
         70 . The method of  claim 59  wherein the increase is about 10%, about 20%, about 30%, about 40%, about 50% or about 60%. 
     
     
         71 . The method of  claim 59 , wherein the patient has breast cancer. 
     
     
         72 . The method of  claim 71 , wherein the breast cancer is ER-positive. 
     
     
         73 . A kit for treating aromatase inhibitor resistant breast cancer comprising a combination of entinostat and a exemestane and instructions for the administration of the dosage form. 
     
     
         74 . The kit of  claim 73 , wherein the kit comprises one entinostat dosage form for every seven aromatase inhibitor dosage forms. 
     
     
         75 . The kit of  claim 73 , wherein the kit comprises one entinostat dosage form for every 14 aromatase inhibitor dosage forms. 
     
     
         76 . The kit of  claim 73 , wherein the kit comprises 4 entinostat dosage forms and 28 aromatase inhibitor dosage forms. 
     
     
         77 . The kit of  claim 73 , wherein the kit comprises 4 entinostat dosage forms and 56 aromatase inhibitor dosage forms. 
     
     
         78 . The method of  claim 59  further comprising administering to the subject one or more therapies in addition to the combination of entinostat and the exemestane selected from the group consisting of: letrozole or anastrozole, or their pharmaceutically acceptable salts, solvates, or prodrugs. 
     
     
         79 . The method of  claim 59  further comprising administering to the subject one or more therapies in addition to the combination of entinostat and the exemestane selected from the group consisting of: radiation therapy, chemotherapy, high dose chemotherapy with stem cell transplant, and monoclonal antibody therapy. 
     
     
         80 . The method of  claim 79  wherein radiation therapy comprises internal and/or external radiation therapy. 
     
     
         81 . The method of  claim 79 , wherein the chemotherapy comprises administering to the subject one or more of doxorubicin, cyclophosphamide, paclitaxel, lapatinib, capecitabine, trastuzumab, bevacizumab, gemcitabine, eribulin, or nab-paclitaxel.