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Related Experiment Videos

Recurrence Score® gene group components and outcomes in the RxPONDER trial (SWOG S1007).

Yara Abdou1, Jess Hoag2, William E Barlow3

  • 1University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Journal of the National Cancer Institute
|July 16, 2026
PubMed
Summary

Racial disparities in breast cancer outcomes persist despite similar Recurrence Score® (RS) results. Analyzing RS gene components reveals variations by ethnicity, suggesting a need to look beyond composite scores for better risk stratification and understanding of these health inequities.

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Area of Science:

  • Oncology
  • Genomics
  • Health Disparities

Background:

  • The RxPONDER trial established adjuvant chemotherapy guidelines for node-positive, hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer.
  • Previous analyses indicated poorer outcomes for non-Hispanic Black (NHB) women compared to non-Hispanic White (NHW) women, despite similar 21-gene Recurrence Score® (RS) results.
  • This suggests that factors contributing to observed disparities may not be fully captured by the composite RS.

Purpose of the Study:

  • To evaluate the individual gene group components of the RS (proliferation, estrogen receptor, HER2, invasion) across different ethnicities, body mass index, and menopausal statuses.
  • To assess the association of these RS components with patient outcomes, specifically invasive disease-free survival (IDFS) and distant recurrence-free interval.

Main Methods:

  • Analysis of 3,102 participants from the RxPONDER trial (HR+/HER2- breast cancer, 1-3 positive nodes, RS ≤ 25) with available ethnicity and gene expression data.
  • Comparison of RS component distributions across ethnic subgroups (NHW, Hispanic, Asian, NHB).
  • Evaluation of associations between RS components and IDFS/distant recurrence-free interval using multivariable Cox models, adjusted for clinicopathologic factors and treatment.

Main Results:

  • RS distributions were generally similar across ethnic groups, with no statistically significant difference in IDFS for NHB versus NHW women (HR 1.41).
  • Tumors from NHB and Hispanic women exhibited higher proliferation scores compared to NHW women.
  • Asian women showed higher HER2 and estrogen receptor (ER) scores and had improved IDFS (HR 0.63) compared to NHW women.

Conclusions:

  • Despite similar overall RS values, the underlying gene expression pathways differ significantly by ethnicity in HR+/HER2- breast cancer.
  • These ethnic variations in proliferation, HER2, and ER pathways may contribute to observed differences in breast cancer outcomes.
  • The findings underscore the importance of evaluating gene-specific biology beyond composite scores like RS to better understand and address health disparities and refine risk stratification.