USE OF ERBB3 INHIBITORS IN THE TREATMENT OF TRIPLE NEGATIVE AND BASAL-LIKE BREAST CANCERS
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.