Methods for treating, preventing and predicting risk of developing breast cancer

1. A method of treating a human subject who has not been diagnosed with breast cancer, wherein the method comprises:

(a) providing a first breast tissue sample from a first human subject who has not been diagnosed with breast cancer and has not undergone a therapy for treatment of breast cancer;

(b) measuring a relative frequency of p27+ breast epithelial cells and a relative frequency of Ki67+ breast epithelial cells in the first breast tissue sample from the first human subject, wherein a relative frequency is calculated as number or % of cells positive for a given marker compared to all breast epithelial cells counted; and

(c) administering a prophylaxis, performing diagnostic assays, and/or periodically monitoring the health of the first human subject having a higher relative frequency of p27+ breast epithelial cells and a higher relative frequency of Ki67+ breast epithelial cells in the first breast tissue sample as compared to a second human subject having a lower relative frequency of p27+ breast epithelial cells and a lower relative frequency of Ki67+ breast epithelial cells in a second breast tissue sample, wherein the second human subject is a control subject known to not have or develop a breast cancer.

2. The method of claim 1 , wherein the first human subject has a BRCA1 mutation.

3. The method of claim 1 , wherein the first human subject has a BRCA2 mutation.

4. The method of claim 1 , further comprising administering to the first human subject a composition comprising an inhibitor of a pathway active in p27+ and/or Ki67+ normal breast epithelial cells.

5. The method of claim 4 , wherein the pathway is selected from the group consisting of cytoskeleton remodeling, chemokines, androgen signaling, cell adhesion, and Wnt signaling.

6. The method of claim 5 , wherein the pathway includes a mediator molecule selected from the group consisting of cyclic AMP (cAMP), epidermal growth factor receptor (EGFR), cyclooxygenase-2 (Cox2), Hedgehog (Hh), Transforming growth factor β receptor (TGFBR), and insulin growth factor receptor (IGFR).

7. The method of claim 5 , wherein the inhibitor selectively targets p27+ breast epithelial cells and/or Ki67+ breast epithelial cells in normal breast tissue.

8. The method of claim 7 , wherein the cells selectively targeted by the inhibitor are also ER+.

9. The method of claim 1 , wherein the first human subject has not been diagnosed with an ER+ breast cancer.

10. The method of claim 1 , wherein the diagnostic assay that is performed on the first human subject in step (c) comprises clinical breast exam, mammography, or MRI.