Genomics and Cancer Biology Metastatic Breast Cancer: Examining the Role of the Tumor Microenvironment Maja Oktay, MD, PhD Professor, Department of Pathology Professor, Department of Anatomy & Structural Biology 718.920.4269 moktay@montefiore.org View Profile Maja Oktay, MD, PhD, studies breast cancer microenvironments responsible for metastasis as well as the effect of chemotherapy on the tumor microenvironment as it relates to metastasis. In particular, the Oktay laboratory focuses on the function of breast cancer intravasation sites called TMEM (Tumor MicroEnvironment of Metastasis) and its interactions with pro-metastatic Mena-expressing tumor cells. Using fine needle aspiration (FNA) biopsy-obtained breast cancer cells from patients, Dr. Oktay determined that cancer cell dissemination markers MenaINV and MenaCalc correlate with TMEM score in estrogen-positive and triple-negative breast cancers from patients, indicating mechanistic involvement of MenaINV, and MenaCalc in TMEM assembly and function in human breast cancer. In addition, using FNA-obtained cancer cells from patients for functional in vitro trans-endothelial migration studies, Dr. Oktay demonstrated that TMEM sites and MenaINV expression in cancer cells are essential for cancer cell trans-endothelial migration in all clinical subtypes of breast cancer. She also participated in the prospective validation study which demonstrated that TMEM score is a predictive marker of metastasis in breast cancer patients, and in a study which demonstrated that TMEM sites are functional sites of transient blood vessel permeability and, as such, the only sites of breast cancer cell intravasation. Dr. Oktay also led a study which established that commonly used chemotherapy for breast cancer can induce TMEM and MenaINV mediated pro-metastatic changes in breast cancer in the neoadjuvant setting, and demonstrated that these changes can be reversed by Tie2 inhibition.