A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores

Breast Cancer Res Treat. 2021 Sep;189(2):455-461. doi: 10.1007/s10549-021-06276-7. Epub 2021 Jun 15.

Abstract

Purpose: A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.

Methods: Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated.

Results: 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows.

Conclusions: The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

Keywords: 21-gene signature assay; 95-gene signature assay; Breast cancer; Estrogen receptor-positive; Recurrence Score.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Chemotherapy, Adjuvant
  • Female
  • Gene Expression Profiling
  • Humans
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics
  • Retrospective Studies

Substances

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