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Understanding The Heterogeneity Of Breast Cancer: Referencing The Normal Breast Luminal Epithelium | 43466
Journal of Clinical & Experimental Pathology
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Breast cancer is a heterogenous group of diseases. Molecular sub-classification has divided it into 5 different subtypes (luminal A
and B, Her2, basal like and triple-negative non-basal). Although this stratification has impacted on breast cancer treatments and
outcomes, patient response to targeted therapy or chemotherapy remains highly unpredictable. Dissection of the normal epithelium is
fundamental to understanding breast cancer heterogeneity. Terminal ductal lobular unit (TDLU) is the primary site where the breast
carcinogenesis initiates. It consists of two types of cells: Luminal epithelium and myoepithelium. Even inside the luminal epithelium,
different cell types are present. For instance, only approximately 10-20% of luminal cells express ER, while majority of the luminal
cells are ER negative. We studied the expression of AR and ER in normal breast luminal cells and found that their distribution pattern
is the same as what was revealed in invasive breast carcinomas indicating that ER/AR positive luminal cells may serve as the “cell
of origin” of ER/AR positive tumors. These different types of luminal cells could subject to different genetic mutations which could
further confound the inter-tumor heterogeneity. We found that Tocopherol-Associated Protein (TAP), a vitamin E binding protein
was co-expressed with ER in normal/benign breast luminal cells but was down regulated in 46% of ER positive breast carcinomas.
This down regulation was associated with poorer clinical outcome in ER positive breast cancer patients. Our study on p53 alteration
in breasts of BRCA carriers and non-carriers revealed that p53 positive normal/benign cells were ER negative luminal cells. We
hypothesis that these cells could serve as the “p53 signature” to predict future risk for a high grade breast carcinoma.
Xi Wang went to Harvard School of Public Health to be the research fellow and later on research associate, after she completed her medical education in the Sun Yet-Sen University Medical School, one of the best medical schools in China. She finished her residency training in pathology in West Virginia University and fellowship training in Sloan-Kettering Cancer Center. She is currently the Associate Professor in Dept. of Pathology in University of Rochester Medical Center, with the major interests in breast and GYN pathology.