Exploring Systemic Physiological Shifts to Understand Breast Cancer Risk

Breast cancers driven by BRCA1 mutations are often aggressive and difficult to treat. Yet, given the lack of reliable biomarkers, we cannot predict when and whether BRCA1 mutant carriers will develop breast cancer. This is because we still lack understanding of how alterations to health throughout an individual’s lifetime interfere with the epigenetic state of BRCA1 mutated “normal” epithelial cells and modulate the timing of cancer development. Recently, studies investigating the cellular heterogeneity of breast tissue from BRCA1-mutant female carriers identified a luminal alveolar cell type that expresses markers of basal breast cells and displays gene expression signatures associated with basal-like breast cancer. These cells, termed Basal-Luminal cells (BL), despite their overall luminal cell identity, are marked by poor transcriptional lineage fidelity, features observed in basal-like breast cancer subtypes, but not yet in cancer-free breast tissue. These and other observations raise the important question regarding the role of BRCA1-mutated BL cells as breast cancer Tumor Initiating Cells (TICs). In this seminar, we will present how studies of normal and BRCA1-deficient mammary tissue—using model systems that induce whole-body physiological changes—have provided insights into the role of BL cells in mammary tumorigenesis.

Complete List of Published Work:
https://www.ncbi.nlm.nih.gov/myncbi/camila.dos%20santos.1/bibliography/public