A total of 140,133 women (median [interquartile range (IQR)] age, 60 [52–67] years) were included for analysis (Table 1). Of these, 115,651 (82.5%), 8,213 (5.9%), 10,814 (7.7%), and 5,455 (3.9%) were NHW, Hispanic, Black, and API women, respectively. Median (IQR) follow up was 66.2 months (48.0–89.8). Baseline characteristics differed significantly among racial and ethnic groups (Table 1). For example, Black women had more patients with progesterone receptor (PR)-negative tumors and grade 3 tumors with RS ≥ 26. API women had more patients with younger than 50 years of age and had private medical insurance with above median income levels.

Logistic MVA showed that, compared with NHW women, Black women were associated with higher RS (≥ 26vs < 26: adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 1.12–1.26, p < 0.001), while HW (aOR 0.93, 95% CI 0.86–1.00, p = 0.04) and API women (aOR 1.03, 95% CI 0.95–1.13, p = 0.45) were not. Patients with lower income, progesterone receptor-negative tumors, LVSI, and higher tumor grades were more likely to have higher RS, while those with more recent year of diagnosis and pN1a tumors were less likely (Table 2).

Cox MVA showed that, compared with NHW women, Black women had worse OS (adjusted hazards ratio [aHR] 1.10, 95% CI 1.02–1.19, p = 0.012), while HW (aHR 0.85, 95% CI 0.77–0.94, p = 0.001) and API (aHR 0.66, 95% CI 0.56–0.77, p < 0.001) women had better OS (Table 3). Variables associated with worse OS were older age, non-private medical insurance, below median income and education levels, more comorbidities, PR-negative status, higher T and N staging, higher tumor grades and RS, LVSI, and positive margin (Table 3). There was a statistically significant interaction between race/ethnicity and RS (interaction p = 0.006). In subgroup analysis, similar findings were noted among those with RS < 26, while only API women were associated with improved OS among others with RS ≥ 26 (Fig. 1).

Forest plot of subgroup analyses for overall survival stratified by racial/ethnic groups and 21-gene recurrence score. Overall survival outcomes were compared stratified by different racial/ethnic subgroups and 21-gene recurrence score. No: number of patients; HR: hazards ratio; 95% CI: 95% confidence interval; RS: 21-gene recurrence score; NHW: non-Hispanic White women

After excluding those with post-diagnosis survival of less than 6 months, Black women still had worse OS (aHR 1.11, 95% CI 1.03–1.19, p = 0.009) compared to NHW women, while HW (aHR 0.85, 95% CI 0.77–0.94, p = 0.002) and API (aHR 0.65, 95% CI 0.56–0.77, p < 0.001) women still had better OS. The interaction between race/ethnicity and RS was also statistically significant (interaction p = 0.006). The findings of the subgroup analysis remained to be similar. Among those with RS < 26, Black women continued to have worse OS (aHR 1.17, 95% CI 1.07–1.28, p < 0.001), while HW (aHR 0.85, 95% CI 0.76–0.96, p = 0.008) and API (aHR 0.73, 95% CI 0.61–0.87, p < 0.001) women continued to have better OS. Among others with RS ≥ 26, only the association of API race with improved OS was significant (aHR 0.48, 95% CI 0.35–0.67, p < 0.001).