A pilot study of tumor-derived exosomes as diagnostic and prognostic markers in breast cancer patients receiving neoadjuvant chemotherapy.

TPS248 Background: Neoadjuvant chemotherapy (NAC) is a common approach to the treatment of women with locally advanced and inflammatory breast cancers. It is becoming utilized in women with palpable and operable tumors >/= 2cm. The rate of response to NAC varies widely and ranges from 2-80%. It may be useful to have markers to determine which patients are most likely to respond to this approach. Tumor derived exosome analysis may be a novel prognostic biosignature in breast cancer. Tumor derived exosomes are membrane-bound endosome-derived vesicles between 50-100 nm which bear protein signatures related to their cell of origin and contain mRNAs and microRNAs. Most cell types including tumor cells secrete them. Exosomes play a role in cell-cell communication and affect target cells by stimulating them directly or by transferring molecules between cells. They have shown promise in early diagnosis in ovarian, colon, prostate and lung cancer but little is known about their role in breast cancer. Methods: Women with palpable and operable breast cancers >/= 2 cm are eligible for this pilot study. The accrual goal is 100 patients. The primary objective is characterization of protein surface markers and RNA profiles of tumor derived exosomes. The secondary objective is correlation of circulating exosome expression with clinical and pathologic response to NAC. Prior to initiation of chemotherapy, patients will undergo collection of 10 ml of whole blood in an EDTA tube for exosome analysis. Exosomes will be extracted from frozen patient plasma. After extraction, half of the extracted sample will be run on the discovery multiplex panel consisting of 45 antibodies. The remaining sample will be used for RNA analysis. Blood collection for exosome analysis will be performed monthly during chemotherapy and following definitive surgery. Subgroup analysis based on tumor size, lymph node status before and after surgery, estrogen, progesterone and HER 2 status are planned.