Contact:
Ronald A. Lubet, Ph.D.
Division Of Cancer Prevention
Telephone: 301-594-0457
Email: rl57q@nih.gov

Objective of Project

The initiative will encourage applications to fund research focused on 1) validating surrogate biomarkers, which can be modulated by chemopreventive agents for ER negative breast cancer employing animal models of non hormonally responsive mammary cancer. The experimental protocols should parallel potential clinical chemoprevention protocols for breast cancer and 2) to identify potential targets which are observed both in human ER negative breast cancer and in hormonally non responsive animal models of breast cancer and to test potential chemopreventive agents directed against these targets. Modulatable surrogate biomarkers are broadly defined and might include gene or protein expression in lesions at risk epithjelium or serum, specific DNA mutations or chromosomal alterations or characteristics associated with imaging (e.g. breast density, nuclear morphometry, etc.) which can be quantitatively altered by an effective chemopreventive agent. One should be able to demonstrate a strong correlation between alteration of the biomarker and the effects of the chemopreventive agent on tumor incidence and multiplicity in the animal model.

Description of Project

The American Cancer Society estimates that this year 193,000 new cases of breast cancer will be diagnosed and that roughly 40,000 women will die of this disease. It is estimated that roughly 25-30% of breast cancers are ER negative and that they will represent 12-17,000 of the deaths associated with breast cancer. Preclinical studies, particularly those performed in animals, were critically important in identifying agents which are now being applied clinically in the field of chemoprevention (e.g. tamoxifen, roloxifene, NSAIDS, celecoxib). Further studies in preclinical models for hormonally non responsive breast cancer are likely to contribute to further definition of potential targets and agents for ER negative disease. Validations of potential modulatable endpoint biomarkers in animal models employing agents or classes of agents with apparent promise for ER negative breast cancer (e.g. COX-2, EGFr, Neu and farnesyltransferase inhibitors) are particularly important. In addition these projects may help to define additional targets and classes of agents that are applicable to ER negative breast cancer. The goals of these studies are to provide surrogate markers and agents for future clinical trials to prevent ER negative breast cancer in women. The combination of an agent that is effective against ER negative breast cancer with an agent effective against ER positive breast cancer (e.g. tamoxifen) is likely to prove a highly effective strategy for reducing breast cancer risk in women.