Methods of Treating Breast Cancer with Anthracycline Therapy

Abstract

The application describes methods for screening subjects with breast cancer to determine if the breast cancer will be responsive to a breast cancer therapy including an anthracycline. The application also describes methods for treating subjects with breast cancer by screening them for the likelihood of the effectiveness of treating the cancer with a therapy including anthracycline and administering the therapy in subjects when it is found that anthracycline is likely to be effective.

What is claimed is: 
     
         1 . A method of screening for the likelihood of the effectiveness of a breast cancer treatment comprising an anthracycline in a subject in need thereof comprising:
 (a) assaying a biological sample obtained from the subject to determine whether or not the biological sample is classified as a Her2+ subtype comprising contacting the biological sample with a probe comprising a detectable label and forming a complex between a nucleic acid or a peptide from the sample with the probe;   (b) assaying the biological sample to determine whether or not the biological sample is classified as a Her-2-E subtype comprising contacting the biological sample with a probe comprising a detectable label and forming a complex between a nucleic acid or a peptide from the sample with the probe; and   (c) providing an assessment of the likelihood of effectiveness of a breast cancer treatment comprising an anthracycline in the subject, wherein if the biological sample is classified as both a Her2+ subtype and a Her-2-E subtype, the breast cancer treatment comprising the anthracycline is more likely to be effective in the subject and wherein if the biological sample is classified as a Her-2-E subtype and is classified as not a Her2+ subtype, the breast cancer treatment comprising the anthracycline is less likely to be effective in the subject.   
     
     
         2 . The method of  claim 1 , wherein assaying the biological sample to determine whether or not the biological sample is classified as a Her2+ subtype is performed using fluorescence in situ hybridization (FISH), enzyme-linked immunosorbent assay (ELISA), Northern blots, FACS analysis, Western blots, or immunohistochemistry (IHC). 
     
     
         3 . The method of  claim 1 , wherein assaying the biological sample to determine whether or not the biological sample is classified as a Her-2-E subtype is performed by detecting the expression levels of a combination of at least 40 genes selected from Table 1, wherein at least 25 of the at least 40 genes comprise FOXA1, MLPH, ESR1, FOXC1, CDC20, ANLN, MAPT, ORC6L, CEP55, MKI67, UBE2C, KNTC2, EXO1, PTTG1, MELK, BIRC5, GPR160, RRM2, SRFP1, MYBL2, NAT1, KIF2C, CXXC5, MIA, and BCL2. 
     
     
         4 . The method of  claim 1 , wherein the anthracycline is selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin, and mitoxantrone. 
     
     
         5 . The method of  claim 4 , wherein the anthracycline is epirubicin. 
     
     
         6 . The method of  claim 1 , wherein the breast cancer treatment comprising anthracycline further comprises one or more anti-cancer agents selected from the group consisting of cyclophosphamide, fluorouracil (or 5-fluorouracil or 5-FU), methotrexate, thiotepa, carboplatin, cisplatin, taxanes, paclitaxel, protein-bound paclitaxel, docetaxel, vinorelbine, tamoxifen, raloxifene, toremifene, fulvestrant, gemcitabine, irinotecan, ixabepilone, temozolmide, topotecan, vincristine, vinblastine, eribulin, mutamycin, capecitabine, capecitabine, anastrozole, exemestane, letrozole, leuprolide, abarelix, buserlin, goserelin, megestrol acetate, risedronate, pamidronate, ibandronate, alendronate, denosumab, zoledronate, trastuzumab, tykerb, and bevacizumab, or combinations thereof. 
     
     
         7 . The method of  claim 1 , wherein the breast cancer treatment comprising anthracycline further comprises one or more anti-cancer agents selected from the group consisting of cyclophosphamide and 5-fluorouracil. 
     
     
         8 . The method of  claim 1 , wherein the breast cancer treatment not comprising anthracycline further comprises one or more anti-cancer agents selected from the group consisting of cyclophosphamide, fluorouracil (or 5-fluorouracil or 5-FU), methotrexate, thiotepa, carboplatin, cisplatin, taxanes, paclitaxel, protein-bound paclitaxel, docetaxel, vinorelbine, tamoxifen, raloxifene, toremifene, fulvestrant, gemcitabine, irinotecan, ixabepilone, temozolmide, topotecan, vincristine, vinblastine, eribulin, mutamycin, capecitabine, capecitabine, anastrozole, exemestane, letrozole, leuprolide, abarelix, buserlin, goserelin, megestrol acetate, risedronate, pamidronate, ibandronate, alendronate, denosumab, zoledronate, trastuzumab, tykerb, and bevacizumab, or combinations thereof. 
     
     
         9 . The method of  claim 1 , wherein the breast cancer treatment not comprising an anthracycline comprises one or more anti-cancer agents of the group consisting of cyclophosphamide, 5-fluorouracil, and methotrexate. 
     
     
         10 . The method of  claim 1 , wherein the biological sample is selected from the group consisting of a cell, tissue, and bodily fluid. 
     
     
         11 . The method of  claim 10 , wherein the tissue is obtained from a biopsy. 
     
     
         12 . The method of  claim 10 , wherein the bodily fluid is selected from the group consisting of blood, lymph, urine, saliva, and nipple aspirate. 
     
     
         13 . A method of treating breast cancer in a subject in need thereof comprising:
 (a) assaying a biological sample obtained from the subject to determine whether or not the biological sample is classified as a basal-like subtype;   (b) providing an assessment of the likelihood of effectiveness of a breast cancer treatment comprising an anthracycline in the subject, wherein if the biological sample is classified as a basal-like subtype, the breast cancer treatment comprising the anthracycline is less likely to be effective in the subject; and   (c) administering a breast cancer treatment not comprising anthracycline to the subject subsequent to said assessment if the biological sample is classified as a basal-like subtype, thereby treating breast cancer in the subject.   
     
     
         14 . The method of  claim 13 , wherein assaying a biological sample obtained from the subject to determine whether or not the biological sample is classified as a basal-like subtype comprises contacting the biological sample with a probe comprising a detectable label and forming a complex between a nucleic acid or a peptide from the sample with the probe. 
     
     
         15 . The method of  claim 13 , wherein assaying the biological sample to determine whether or not the biological sample is classified as a basal-like subtype is performed by detecting the expression levels of a combination of at least 40 genes selected from Table 1, wherein at least 25 of the at least 40 genes comprise FOXA1, MLPH, ESR1, FOXC1, CDC20, ANLN, MAPT, ORC6L, CEP55, MKI67, UBE2C, KNTC2, EXO1, PTTG1, MELK, BIRC5, GPR160, RRM2, SRFP1, MYBL2, NAT1, KIF2C, CXXC5, MIA, and BCL2. 
     
     
         16 . The method of  claim 13 , wherein the anthracycline is selected from the group consisting of daunorubicin, doxorubicin, epirubicin, idarubicin, valrubicin, and mitoxantrone. 
     
     
         17 . The method of  claim 16 , wherein the anthracycline is epirubicin. 
     
     
         18 . The method of  claim 13 , wherein the breast cancer treatment comprising anthracycline further comprises one or more anti-cancer agents selected from the group consisting of cyclophosphamide, fluorouracil (or 5-fluorouracil or 5-FU), methotrexate, thiotepa, carboplatin, cisplatin, taxanes, paclitaxel, protein-bound paclitaxel, docetaxel, vinorelbine, tamoxifen, raloxifene, toremifene, fulvestrant, gemcitabine, irinotecan, ixabepilone, temozolmide, topotecan, vincristine, vinblastine, eribulin, mutamycin, capecitabine, capecitabine, anastrozole, exemestane, letrozole, leuprolide, abarelix, buserlin, goserelin, megestrol acetate, risedronate, pamidronate, ibandronate, alendronate, denosumab, zoledronate, trastuzumab, tykerb, and bevacizumab, or combinations thereof. 
     
     
         19 . The method of  claim 13 , wherein the breast cancer treatment comprising anthracycline further comprises one or more anti-cancer agents selected from the group consisting of cyclophosphamide and 5-fluorouracil. 
     
     
         20 . The method of  claim 13 , wherein the breast cancer treatment not comprising anthracycline further comprises one or more anti-cancer agents selected from the group consisting of cyclophosphamide, fluorouracil (or 5-fluorouracil or 5-FU), methotrexate, thiotepa, carboplatin, cisplatin, taxanes, paclitaxel, protein-bound paclitaxel, docetaxel, vinorelbine, tamoxifen, raloxifene, toremifene, fulvestrant, gemcitabine, irinotecan, ixabepilone, temozolmide, topotecan, vincristine, vinblastine, eribulin, mutamycin, capecitabine, capecitabine, anastrozole, exemestane, letrozole, leuprolide, abarelix, buserlin, goserelin, megestrol acetate, risedronate, pamidronate, ibandronate, alendronate, denosumab, zoledronate, trastuzumab, tykerb, and bevacizumab, or combinations thereof. 
     
     
         21 . The method of  claim 13 , wherein the breast cancer treatment not comprising an anthracycline comprises one or more anti-cancer agents of the group consisting of cyclophosphamide, 5-fluorouracil, and methotrexate. 
     
     
         22 . The method of  claim 13 , wherein the biological sample is selected from the group consisting of a cell, tissue, and bodily fluid. 
     
     
         23 . The method of  claim 22 , wherein the tissue is obtained from a biopsy. 
     
     
         24 . The method of  claim 22 , wherein the bodily fluid is selected from the group consisting of blood, lymph, urine, saliva, and nipple aspirate.