Postpartum breast cancer has a distinct molecular profile that predicts poor outcomes

Nat Commun. 2021 Nov 3;12(1):6341. doi: 10.1038/s41467-021-26505-3.

Abstract

Young women's breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5-10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast / abnormalities
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Cycle
  • Cell Proliferation
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, p53 / genetics
  • Humans
  • Hypertrophy
  • Immunity
  • Middle Aged
  • Mutation
  • Postpartum Period / genetics*
  • Postpartum Period / metabolism*
  • Pregnancy
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Transcriptome
  • Tumor Microenvironment / genetics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Receptors, Estrogen
  • TP53 protein, human
  • Tumor Suppressor Protein p53

Supplementary concepts

  • Gigantomastia