Evaluation of DNA Methylation as a Target for Intraductal Therapy for Ductal Carcinoma in Situ of the Breast

摘要

In ductal carcinoma in situ(DCIS), the malignant cells are confined within the basement membrane, and so an ideal candidate for local therapies. Because DNA methylation is a potentially reversible mechanism for tumor suppressor gene inactivation, it is an intriguing target for molecular therapeutics. In this study we have documented significant methylation in eight tumor suppressor genes in DCIS. We have successfully performed ductal lavage in 24/27 patients undergoing surgery for DCIS without any complications. Unfortunately, we were able to successfully identify and lavage the malignant duct in only 25% of cases, half of which were identified because the patient presented with discharge. In the absence of nipple discharge, only 14% of the lavaged ducts were the malignant duct. While these data do not rule out the potential of targeting DNA methylation for intraductal therapy for DCIS, we need better methods for identifying the malignant ductal orifices before proceeding to clinical trials of intraductal therapy.