MicroRNA-Based Methods and Compositions for the Diagnosis, Prognosis and Treatment of Breast Cancer

Abstract

The present invention provides novel methods and compositions for the diagnosis, prognosis and treatment of breast cancer. The invention also provides methods of identifying anti-breast cancer agents.

What is claimed is: 
     
         1 . A pharmaceutical composition for treating breast cancer, comprising at least one isolated miR gene product, and a pharmaceutically-acceptable carrier;
 wherein the at least one isolated miR gene product is selected from the group consisting of: miR-145, miR-10b, miR-123 (miR-126), miR-140-as, miR-125a, miR-125b-1, miR-125b-2, miR-194, miR-204, let-7a-2, let-7a-3, let-7d (let-7d-v1), let-7f-2, miR-101-1, miR-143 and combinations thereof.   
     
     
         2 . A pharmaceutical composition for treating breast cancer, comprising at least one miR expression inhibitor compound, and a pharmaceutically-acceptable carrier:
 wherein the at least one miR inhibitor compound is selected from the group consisting of miR-21, miR-155, miR-009-1 (miR-131-1), miR-34 (miR-170), miR-102 (miR-29b), miR-213, let-7i (let-7d-v2), miR-122a, miR-128b, miR-136, miR-149, miR-191, miR-196-1, miR-196-2, miR-202, miR-203, miR-206, miR-210, miR-213 and combinations thereof.   
     
     
         3 . A pharmaceutical composition for treating breast cancer, comprising at least one isolated miR gene product, wherein the breast cancer is associated with one or more prognostic markers and the at least one miR gene product are selected from the group consisting of:
 (i) the breast cancer is a breast cancer associated with estrogen receptor expression and the miR gene product is selected from the group consisting of miR-26a, miR-26b, miR-102 (miR-29b), miR-30a-5p, miR-30b, miR-30c, miR-30d, miR-185, miR-191, miR-206, miR-212, and combinations thereof;   (ii) the breast cancer is a breast cancer associated with progesterone receptor expression and the miR gene product is selected from the group consisting of let-7c, miR-26a, miR-29b, miR-30a-5p, miR-30b, miR-30c, miR-30d, and combinations thereof;   (iii) the breast cancer is a breast cancer associated with positive lymph node metastasis and the miR gene product is selected from the group consisting of let-7f-1, let-7a-3, let-7a-2, miR-9-3, and combinations thereof;   (iv) the breast cancer is a breast cancer associated with a high proliferative index and the miR gene product is selected from the group consisting of let-7c, let-7d, miR-26a, miR-26b, miR-30a-5p, miR-102, miR-145, and combinations thereof;   (v) the breast cancer is a breast cancer associated with detectable p53 expression and the miR gene product is selected from the group consisting of miR-16a, miR-128b and a combination thereof;   (vi) the breast cancer is a breast cancer associated with high vascular invasion and the miR gene product is selected from the group consisting of miR-9-3, miR-10b, miR-27a, miR-29a, miR-123, miR-205 and combinations thereof; and   (vii) the breast cancer is a breast cancer associated with an advanced tumor stage and the miR gene product is selected from the group consisting of miR-9-2, miR-15-a, miR-21, miR-30a-s, miR-133a-1, miR-137, miR-153-2, miR-154, miR-181a, miR-203, miR-213, and combinations thereof.