Racial/ethnic differences in 21-gene recurrence score and survival among estrogen receptor-positive breast cancer patients.
Authors: Gill Jasmin , Ma Sung Jun , Yendamuri Keerti , Chatterjee Udit , Yao Song , Oladeru Oluwadamilola Temilade , Singh Anurag K. 
Published: June 2023

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Background: Despite studies on racial/ethnic disparities in breast cancer patients, there is limited literature evaluating association of racial/ethnic differences with 21-gene recurrence score (RS) and survival differences stratified by RS risk categories. We performed an observational cohort study to evaluate such disparities in context of RS. Methods: The National Cancer Database (NCDB) was queried for patients with ER-positive, pT1-3N0-1aM0 breast cancer who received surgery followed by adjuvant endocrine therapy with available RS from 2006 to 2018. Racial/ethnic groups were stratified by non-Hispanic White (NHW), Hispanic White (HW), Black, and Asian/Pacific Islander (API). Our primary endpoint was overall survival (OS). Logistic multivariable analysis (MVA) was built upon baseline patient and tumor characteristics to evaluate variables associated with RS > 25. Cox MVA was used to evaluate OS. Interaction term analysis was used to identify heterogeneous association of racial/ethnic groups and RS; if significant, subgroup analyses compared magnitude of racial/ethnic differences stratified by RS. To address immortal time bias, Cox MVA analyses were repeated after excluding patients with post-diagnosis survival < 6 months. P values were two-sided. Bonferroni correction was used for multiple comparisons (NHW vs HW women, NHW vs Black women, and NHW vs API women) with p values less than 0.017 being statistically significant. Results: A total of 140,133 women (median [interquartile range (IQR)] age, 60 [52-67] years) were included for analysis. 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 mo. (48.0-89.8). Logistic MVA showed compared to NHW women, Black women were associated with higher RS (26 or higher vs < 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 (aOR 1.03, 95% CI 0.95-1.13, p = 0.45) were not. Cox MVA showed compared to NHW, Black women were associated with 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) were not. There was significant interaction between race/ethnicity and RS (interaction p = 0.006). Subgroup analysis found similarities in those with RS < 26, while only API women were associated with improved OS among those with RS ≥ 26. After excluding those with post-diagnosis survival < 6 mo., our findings remained comparable. Conclusions: To our knowledge, this is the largest nationwide oncology database study to suggest that Black women are associated with higher RS, while HW and API are not. It also suggests that Black women are associated with worse OS among those with RS < 26, while API are associated with improved OS regardless of RS compared to NHW women.