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

The RxPONDER trial has guided adjuvant chemotherapy use in node-positive HR+/HER2- breast cancer; however, prior analyses showed poorer outcomes among non-Hispanic Black (NHB) women compared with non-Hispanic White (NHW) women despite similar 21-gene Recurrence Score (RS) results. This suggests contributors to disparities may not be captured by the composite RS. We evaluated RS gene group components-proliferation, estrogen receptor (ER), HER2 (GRB7), and invasion-by ethnicity, body mass index, and menopausal status, and we assessed associations with outcomes.

RxPONDER enrolled 5083 women with HR+/HER2- breast cancer, 1-3 positive nodes, and RS ≤25, randomly assigned to endocrine therapy ± chemotherapy. In total, 3102 participants with ethnicity and gene expression data were included. RS components were compared across subgroups, and associations with invasive disease-free survival (IDFS) and distant recurrence-free interval were evaluated by using multivariable Cox models adjusted for clinicopathological factors and treatment.

Among 3102 women (70.2% NHW, 15.5% Hispanic, 9.5% Asian, 4.7% NHB), RS distributions were similar across groups and prognostic overall. Tumors from NHB (P = .003) and Hispanic women (P = .02) had higher proliferation scores vs NHW women, and Asian women had higher HER2 (P = .006) and ER scores (P = .028). IDFS differences were not statistically significant for NHB vs NHW women (hazard ratio [HR] = 1.41, 95% CI = 0.98 to 2.03), whereas Asian women had improved IDFS (HR = 0.63, 95% CI = 0.43 to 0.91).

Despite similar overall RS distributions, component pathways vary by ethnicity and may contribute to outcome differences. These findings support evaluating gene-specific biology beyond composite scores to better understand disparities and refine risk stratification.

ClinicalTrials.gov: NCT01272037.