Use of erbb3 inhibitors in the treatment of triple negative and basal-like breast cancers

Abstract

Provided are methods of suppressing growth of triple negative breast tumors and basal-like breast tumors by contacting tumor cells with an ErbB3 inhibitor, e.g., an anti-ErbB3 antibody. Also provided are methods for treating triple negative breast cancer or basal-like breast cancer in a patient by administering to the patient an ErbB3 inhibitor, e.g., an anti-ErbB3 antibody. The treatment methods can further comprise selecting a patient having a triple negative breast cancer or basal-like breast cancer and then administering an ErbB3 inhibitor to the patient. The treatment methods also can further comprise administering at least one additional anti-cancer agent to the patient in combination with the ErbB3 inhibitor.

1 . A method of suppressing growth of triple negative breast cancer cells in a patient having a tumor that is identified as triple negative breast cancer, the method comprising administering to the patient an effective amount of an anti-ErbB3 antibody, or antigen-binding fragment thereof, comprising a V H  CDR1 sequence of SEQ ID NO:3, a V H  CDR2 sequence of SEQ ID NO:4 and a V H  CDR3 sequence of SEQ ID NO:5, and a V L  CDR1 sequence of SEQ ID NO:6, a V L  CDR2 sequence of SEQ ID NO:7 and a V L  CDR3 sequence of SEQ ID NO:8. 
     
     
         2 . The method of  claim 1 , wherein the anti-ErbB3 antibody comprises a V H  sequence as shown in SEQ ID NO:1 and a V L  sequence as shown in SEQ ID NO:2. 
     
     
         3 . The method of  claim 1 , wherein the triple negative breast cancer tumor is histopathologically characterized as having a basal-like phenotype. 
     
     
         4 . The method of  claim 1 , wherein the triple negative breast cancer tumor is histopathologically characterized as having a phenotype other than basal-like. 
     
     
         5 . The method of  claim 1 , which further comprises administering to the patient an effective amount of at least one additional anti-cancer agent. 
     
     
         6 . The method of  claim 5 , wherein the at least one additional anti-cancer agent is selected from the group consisting of platinum-based chemotherapy drugs, taxanes, tyrosine kinase inhibitors, anti-EGFR antibodies, and combinations thereof. 
     
     
         7 . The method of  claim 6 , wherein the at least one additional anti-cancer agent is a taxane. 
     
     
         8 . The method of  claim 5 , wherein the at least one additional anti-cancer agent comprises an EGFR inhibitor. 
     
     
         9 . The method of  claim 8 , wherein the EGFR inhibitor comprises an anti-EGFR antibody. 
     
     
         10 . The method of  claim 9 , wherein the anti-EGFR antibody is selected from the group consisting of cetuximab, matuzumab, panitumumab, nimotuzumab and mAb 806. 
     
     
         11 . The method of  claim 8 , wherein the EGFR inhibitor is a small molecule inhibitor of EGFR signaling selected from the group consisting of gefitinib, lapatinib, and erlotinib HCL. 
     
     
         12 . The method of  claim 5 , wherein the at least one additional anti-cancer agent comprises a VEGF inhibitor. 
     
     
         13 . The method of  claim 12 , wherein the VEGF inhibitor comprises bevacizumab. 
     
     
         14 . The method of  claim 1 , wherein the triple negative breast cancer tumor scores negative for estrogen receptor (ER) and progesterone receptor and yields a test result of 0, 1+, or 2+ using a semi-quantitative immunohistochemical assay using a polyclonal anti-HER2 primary antibody. 
     
     
         15 . The method of  claim 14 , wherein the tumor is FISH negative for HER2 gene amplification. 
     
     
         16 . A method of suppressing growth of triple negative breast cancer cells in a patient, the method comprising:
 1) identifying a patient with a triple negative breast cancer tumor, and   2) administering to the patient an effective amount of an anti-ErbB3 antibody, or antigen-binding fragment thereof, comprising a V H  CDR1 sequence of SEQ ID NO:3, a V H  CDR2 sequence of SEQ ID NO:4 and a V H  CDR3 sequence of SEQ ID NO:5, and a V L  CDR1 sequence of SEQ ID NO:6, a V L  CDR2 sequence of SEQ ID NO:7 and a V L  CDR3 sequence of SEQ ID NO:8.   
     
     
         17 . The method of  claim 16 , wherein the anti-ErbB3 antibody comprises a V H  sequence as shown in SEQ ID NO:1 and a V L  sequence as shown in SEQ ID NO:2. 
     
     
         18 . The method of  claim 16 , wherein the triple negative breast cancer tumor scores negative for estrogen receptor (ER) and progesterone receptor and yields a test result of 0, 1+, or 2+ using a semi-quantitative immunohistochemical assay using a polyclonal anti-HER2 primary antibody. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 16 , which further comprises administering to the patient an effective amount of at least one additional anti-cancer agent. 
     
     
         22 . The method of  claim 21 , wherein the at least one additional anti-cancer agent is a taxane.