Inflammatory Milieu Permits Metastasis in Pregnancy-Associated Breast Cancer

摘要

Background and Hypothesis: Pregnancy associated breast cancer (PABC) has higher metastatic potential. We propose that the process of mammary gland involution following pregnancy co-opts programs of wound healing and this pro- inflammatory milieu promotes metastasis. The following aims are proposed. Aim 1. Validate in human breast tissue that breast involution has a pro- inflammatory component. Results: CD45 and CD68 positive cells are increased in human involuting brnasts consistent with a pro-inflammatory program. Aim 2. Investigate the hypothesis that PABC in women will be characterized by expression of negative prognostic stromal markers (desmoplasia) and correlate with clinical data and outcomes. Results: work to begin year 2. Aim 3. Using animal models for human PABC determine whether mammary tumors that develop in the context of involution have increased desmoplasia and metastases. Results: Four new models for PABC are in development with promising preliminary results. Impact on Breast Cancer Research and Patients: The identification of mammary gland involution as the mediator of PABC metastasis identifies a new window for targeted therapies directed at decreasing the pro-inflammatory milieu of the involuting breast.