Therapeutic treatment of breast cancer based on c-maf status

Abstract

The present invention relates to the design of a customized therapy for a subject with breast cancer based on the c-MAF expression level and the menopausal status of the subject. In some embodiments, the customized therapy comprises an agent for avoiding or preventing bone degradation. In some embodiments, the agent for avoiding or preventing bone degradation is zoledronic acid.

1 - 46 . (canceled) 
     
     
         47 . An in vitro method for predicting IDFS excluding bone recurrence of a patient with breast cancer which comprises determining the c-MAF gene expression level, copy number, amplification, or gain in a tumor sample of said subject relative to a reference wherein an increase of the c-MAF gene expression level, copy number, amplification, or gain with respect to said reference is indicative of poor IDFS excluding bone recurrence. 
     
     
         48 - 78 . (canceled) 
     
     
         79 . A method for the treatment of a subject having breast cancer which comprises:
 i) quantifying the c-MAF gene expression level, copy number, amplification, or gain in a tumor sample of said subject and   ii) comparing the expression level, copy number, amplification, or gain obtained in i) with a reference value,   wherein said subject has a not increased expression level, copy number, amplification, or gain with respect to said reference value, and administering to said subject a therapy comprising an estrogen receptor modulator.   
     
     
         80 . The method of  claim 79 , wherein the subject is non-postmenopausal or postmenopausal. 
     
     
         81 . The method of  claim 79 , wherein the subject is further administered a therapy aiming to prevent and/or treat bone remodeling, improve disease free survival or overall survival. 
     
     
         82 . The method according to  claim 79 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor. 
     
     
         83 . The method according to  claim 79 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-l-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethylpropanoate, and SH646. 
     
     
         84 . The method of  claim 79 , wherein the breast cancer is selected from the group consisting of: ER+ breast cancer, ER− breast cancer, triple negative breast cancer, of the basal-like subtype, and HER2+ breast cancer. 
     
     
         85 . A method for the treatment of bone metastasis in a subject having breast cancer comprising determining that said subject has a non increased c-MAF expression level, amplification, copy number or gain in a tumor sample with respect to a control sample and administering to said subject an agent capable of preventing or inhibiting bone remodeling or improving disease free survival or overall survival, wherein the agent capable of preventing or inhibiting bone remodeling or improving disease free survival or overall survival is an estrogen receptor modulator. 
     
     
         86 . The method of  claim 85 , wherein the subject is postmenopausal. 
     
     
         87 . The method of  claim 85 , wherein the breast cancer is selected from the group consisting of: ER+ breast cancer, ER− breast cancer, triple negative breast cancer, of the basal-like subtype, and HER2+ breast cancer. 
     
     
         88 . The method of  claim 85 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor. 
     
     
         89 . The method of  claim 85 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethylpropanoate and SH646. 
     
     
         90 . A method for the treatment of a subject having breast cancer comprising determining that said subject has a non increased c-MAF expression level, amplification, copy number, or gain in a tumor sample with respect to a control sample, and administering to said subject an agent, and wherein the agent is an estrogen receptor modulator. 
     
     
         91 . The method of  claim 90 , wherein the subject is non-postmenopausal, premenopausal or postmenopausal. 
     
     
         92 . The method of  claim 90 , wherein the breast cancer is selected from the group consisting of: ER+ breast cancer, ER− breast cancer, triple negative breast cancer, of the basal-like subtype, and HER2+ breast cancer. 
     
     
         93 . The method of  claim 90 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor. 
     
     
         94 . The method according to  claim 90 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethylpropanoate and SH646. 
     
     
         95 . A method for the identification of a subject having breast cancer who will benefit from treatment with an agent comprising:
 i) quantifying the c-MAF gene expression level, copy number, amplification, or gain in a tumor sample of said subject and   ii) comparing the expression level, copy number, amplification, or gain obtained in i) with a reference value,   wherein said subject has an increased expression level, copy number, amplification, or gain with respect to said reference value, and administering to said subject an agent, wherein the agent is an estrogen receptor modulator.   
     
     
         96 . The method of  claim 95 , wherein the breast cancer is selected from the group consisting of: ER+ breast cancer, ER− breast cancer, triple negative breast cancer, of the basal-like subtype, and HER2+ breast cancer. 
     
     
         97 . The method of  claim 95 , wherein the estrogen receptor modulator inhibits the binding of estrogen to the estrogen receptor. 
     
     
         98 . The method according to  claim 95 , wherein the estrogen receptor modulator is selected from the group consisting of progestogen, estradiol, droloxifene, raloxifiene, lasofoxifene, TSE-424, tamoxifen, idoxifene, LY353381, LY117081, toremifene, fulvestrant, 4-[7-(2,2-dimethyl-1-oxopropoxy-4-methyl-2-[4-[2-(1-piperidinyl)ethoxy]phenyl]-2H-1-benzopyran-3-yl]-phenyl-2,2-dimethylpropanoate and SH646.