Breast Cancer Prevention by Inducing Apoptosis in DCIS Using Breast Ductal Lavage
Annual rept. 1 Sep 2005-31 Aug 2006
WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
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Current prevention focuses on oral administration of chemopreventive agents which decreases breast cancer incidence but increases the risk for secondary treatment-induced disease. In addition, these chemopreventive agents may not be effective in preventing those lesions that are estrogen receptor ER negative. We hypothesize that programmed cell death is dysregulated in premalignant breast cells which permits these cells to avoid cell death. We are currently investigating whether treating premalignant breast cells with a molecular genetic-based agent may be effective alone or in concert with tamoxifen treatment to induce cell death in both ER-positive and ER-negative cells. Our preliminary studies indicate a DCIS primary explant cell line overexpresses the anti-apoptotic proteins Bcl-2 and Bcl-xL compared to normal breast tissue. Our initial studies also show an increase in programmed cell death in the DCIS primary explant cell line after treatment with an antisense bcl-2bcl-xl andor tamoxifen. Ultimately, we envision delivering genetic-based preventive agents andor a chemopreventive agent directly to the breast ductal lobe of these high risks eliminating any potential for secondary treatment-induced disease.
- Medicine and Medical Research