Intrinsic subtypes and genomic signatures of primary breast cancer and prognosis after systemic relapse

Mol Oncol. 2016 Apr;10(4):517-25. doi: 10.1016/j.molonc.2015.11.004. Epub 2015 Nov 18.


Molecular subtypes and gene expression signatures are widely used in early breast cancer but their role in metastatic disease is less explored. Two hundred-twenty patients diagnosed with primary breast cancer and subsequent relapse in Stockholm, Sweden between 1997 and 2006 were identified and their primary tumor was assessed for immunohistochemistry (IHC)- and PAM50-based subtypes, risk of recurrence (ROR-S) score, 21-gene and 70-gene signatures using research-based microarray expression profiles. Clinical and pathological data were retrospectively collected. Post-relapse survival within intrinsic subtypes and genomic signatures was investigated by Kaplan-Meier and Cox regression methods. ROR weighted for proliferation index (ROR-P) was explored and the prognostic contribution provided when combined to a clinical model estimated as change in LR- χ(2). IHC classified 27%, 24%, 36% and 13% of the tumors as luminal A, luminal B, HER2+ and triple negative, respectively. PAM50 categorized 22%, 24%, 26%, 22%, 6% of the tumors as luminal A, luminal B, HER2-enriched, basal-like and normal-like. Triple negative and basal tumors had a significantly shorter median post-relapse survival in comparison with luminal. Overall, neither IHC nor PAM50 subtypes, 21- and 70- gene profiles were prognostic in multivariable models. Low and medium ROR-S had a longer survival compared with the high-risk group (23 vs 10 months; p = 0.04). ROR-P independently correlated with post-relapse survival (p = 0.002) and provided the most significant prognostic information when added to a clinical model. ROR score from primary tumor represents an independent prognostic factor of post-relapse survival beyond classical clinical and pathological variables.

Keywords: Gene expression signature; Intrinsic subtypes; Metastatic breast cancer; Proliferation score; Risk of recurrence score.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Breast Neoplasms* / therapy
  • Cell Proliferation*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Recurrence, Local* / metabolism
  • Neoplasm Recurrence, Local* / mortality
  • Neoplasm Recurrence, Local* / pathology
  • Neoplasm Recurrence, Local* / therapy
  • Retrospective Studies
  • Survival Rate


  • Neoplasm Proteins