Classification of PR-positive and PR-negative subtypes in ER-positive and HER2-negative breast cancers based on pathway scores

摘要

PR loss in ER /HER2- breast cancer indicates worse prognosis and insensitivity to anti-estrogen therapy, while the mechanisms of PR loss in ER /HER2- breast cancer remain unrevealed. In this study, ER /PR /HER2- and ER /PR-/HER2- breast cancer cases from TCGA were used. 1387 pathways were analyzed and used as variables for classifying the two groups with LASSO regression. ER /PR /HER2- and ER /PR-/HER2- breast cancer groups can be classified by a combination of 13 pathways using their activity score. Among the 13 pathways, those involving growth factors and ion-channel transporters were most significant in the distinction, followed by pathways involving immune modulation and cell metabolism. Two growth factor pathways, EGF and IGF-1, were deferentially regulated in ER /PR /HER2- and ER /PR-/HER2- groups. In conclusion, this study indicated in ER /HER2- breast cancers the various status of PR expression can be an indication of molecular variation, particularly for the growth factor pathway activation.