Breast Cancer Precursors: Perturbations of Mammary Epithelial Cell Identity as a Response to Abnormal Signaling from Stromal Compartment

Abstract

Despite outstanding progress over the past few years, breast cancer remains the second leading cause of cancer-related death among women. This fact emphasizes the need for effective preventive intervention. Accumulating evidence indicates that epigenetic control of gene expression plays a fundamental role in mammary tissue homeostasis, and suggests that alterations in such a fine control may affect epithelial cell identity and trigger neoplastic transformation. Therefore, understanding the biological basis of breast cancer initiation is of paramount importance to prevent pathologic alterations leading to the emergence of premalignant lesions that potentially could evolve into invasive cancer. In this overview, we described and discussed some recent findings from two early breast cancer precursors, hyperplastic enlarged lobular unit (HELU) and atypical ductal hyperplasia (ADH), in which we investigated the pattern of expression of a panel of genes involved in the control of cell identity and mammary gland remodeling, compared to the corresponding histologically normal tissue. Collectively, findings suggest that the changes in cell identity associated with HELU and ADH development are likely due to alterations in the epigenetic control of gene transcription and that a possible cause for the occurring of these alterations could be an abnormal and/or persistent ovarian hormone signaling from surrounding microenvironment . Since, unlike genetic alterations, epigenetic changes are potentially reversible, in the last part of the overview, some epigenome-targeting strategies, potentially useful strategy for cancer prevention are proposed and discussed.