Early Detection of Breast Cancer by Molecular Analysis of Ductal Lavage Fluid

Abstract : Reliable intermediate biological markers for breast cancer risk, that can be easily detected in both pre- and post- menopausal women, do not exist at the present time. For more than 20 years, the ability to access breast ductal fluid through the nipple has prompted initiatives to develop a PAP-like test for breast cancer. Yields were variable, not every woman yielded fluid, and there was no assurance of obtaining samples from the entire length of the ducts. In this proposal, we will use a 1) a facile ductal lavage (DL) technique using cannulating catheters which flushes each duct to yield thousands of ductal cells. 2) a panel of markers consisting of three genes, Cyclin D2, Twist and retinoic acid receptor beta 2 (RAR beta 2), which are aberrantly hypermethylated in breast cancer cells. We will standardize the techniques using fluid from cancer patients, and then evaluate the frequency of cells positive by MSP assays in ductal lavage obtained from women with a high risk of developing breast cancer, such as patients with lobular carcinoma, patients with cancer in one breast, and those with mammographically suspicious lesions. Thus, we aim to develop a PAP test for the breast.