Breast Cancer Prevention by Inducing Apoptosis in DCIS Using Breast Ductal Lavage

Abstract

Abstract : Although great strides have been made in breast cancer screening and treatment, it remains the second highest cause of cancer-related deaths for women in the United States. Current prevention has focused on oral administration of tamoxifen which appears to decrease breast cancer incidence but increases the risk for secondary uterine cancer. In addition, tamoxifen may not be effective in preventing those lesions that are estrogen receptor (ER) negative based on its primary function of suppressing cell proliferation by blocking the estrogen receptor. WE hypothesize that programmed cell death (PCD) is dysregulated in premalignant and malignant breast cells which permits both ER-positive and ER-negative cells to avoid cell death. We intend to investigate whether treating premalignant breast cells with a molecular genetic-based agent (antisense bcl-2/bcl-xL oligonucleotide) may be effective alone or in concert with tamoxifen treatment to induce cell death in both ER-positive and ER-negative cells. Ultimately, we envision using the newly developed technique of breast ductal lavage to not only screen women for increased risk in developing breast cancer, which is currently being performed, but to, also use this technique to delivery genetic-based preventive agents and/or tamoxifen directly to the breast ductal lobe of these high risk individuals thus eliminating any potential for tamoxifen-induced uterine cancers.