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

BMC Med Res Methodol. 2021 May 22;21(1):108. doi: 10.1186/s12874-021-01297-8.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Estrogen receptor, Progesterone receptor; Growth factor; LASSO; Pathway activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor
  • Breast Neoplasms* / diagnosis
  • Female
  • Humans
  • Prognosis
  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2