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

摘要

Current prevention focuses on oral administration of chemopreventive agents which decreases breast cancer incidence but increases the risk for secondary treatment-induced disease and 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. Our studies indicate the ductal carcinoma in situ cell line DCIS3A overexpresses the anti-apoptotic proteins Bcl-2 and Bcl-xL compared to normal breast tissue. In addition, we have shown that DCIS3a treated with a bispecific antisense oligonucleotide against bcl-2 and bcl-xl down regulates expression of both proteins. These studies also show an increase in programmed cell death in the DCIS3A cell line after treatment with the bispecific antisense oligo bcl-2/bcl-xl alone but not with tamoxifen alone nor a synergic effect in combination with the antisense oligo. Finally, cells obtained from breast ductal lavage appear to express BCL-2, BCL-XL, and BAX which suggests these cells may be already avoiding programmed cell death.