Recurrence score gene axes scores and outcomes by race and ethnicity in the RxPONDER trial.
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515 Background: Racial inequities in breast cancer outcomes remain a significant healthcare concern. In a previous analysis of the RxPONDER trial by race/ethnicity, we showed that non-Hispanic Black (NHB) women have worse outcomes compared to non-Hispanic Whites (NHW) despite similar 21-gene recurrence scores (RS). The RS is determined by an assay consisting of 16 cancer-related genes involved in invasion, ER and HER2 signaling, and proliferation. To provide a better understanding of the differences in underlying tumor biology amongst different racial/ethnic groups, we analyzed RS gene axes scores amongst each group and associations with outcomes. Methods: A total of 3,102 women were included: Hispanic (15.5%), NHB (4.7%), Asian (9.5%), and NHW (70.2%). The primary outcome was invasive disease-free survival (IDFS). This analysis extends median follow-up from 5 to 7 years and evaluates gene axes scores that are components of the RS by race/ethnicity. Impact of proliferation, ER, GRB7 (HER2), and invasion axes scores on IDFS was evaluated in Cox regression models. Results: There were no differences in RS distribution across racial/ethnic groups, and RS remained prognostic for each group with no significant variation in RS prognostic value. However, NHBs were noted to have significantly higher proliferation axis scores than NHWs (p<0.001); HER2 axis scores was higher for Asians than NHWs (p<0.001); and Hispanics had both higher HER2 (p=0.002) and proliferation (p=0.02) axes scores compared to NHWs. These results remained statistically significant after adjusting for age. Relative to NHWs, IDFS was worse for NHBs (HR 1.41; 95% CI 0.98-2.03) and better for Asians (HR 0.63; 95% CI 0.43-0.91) in unadjusted analysis. Adjusting for treatment arm, age, grade, menopausal status, proliferation, ER and HER2 axes scores attenuated the impact of race on IDFS for NHBs (HR 1.22; 95% CI 0.84-1.76), although the findings were unchanged for Asians (HR 0.64; 95% CI 0.44-0.93; Table). In a multivariable model, proliferation axis (HR 1.56; 95% CI 1.35-1.80) and ER axis (HR 0.81; 95% CI 0.71-0.93) were prognostic for IDFS. Conclusions: RS gene axes scores differ by race/ethnicity with higher proliferation axis scores noted in NHBs, which could partially explain their inferior outcomes noted in RxPONDER. These findings suggest that tumor biology is indeed important, however, we must dig deeper to uncover intricate factors that contribute to disparities, which is key to designing comprehensive strategies to address them. Clinical trial information: NCT01272037 . [Table: see text]
