Disparities within luminal breast cancer: Clinical and molecular features of African American and non-Hispanic white patients.
Authors: Hoskins Kent , Danciu Oana Cristina , Gadi Vijayakrishna K. , Simons Yael , Blumencranz Lisa Eileen , Kling Heather , Uygun Sahra , Crozier Jennifer A. , Habibi Mehran , Sharma Dipali , Audeh William ,   FLEX Investigators Group
Published: June 2021

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Background: African American breast cancer patients (AA) are diagnosed younger, have more high-risk features, and poorer clinical outcomes than non-Hispanic White patients (NHW), despite similar treatments. Although comorbidities such as obesity and metabolic syndrome may contribute to differences, ancestry-specific factors and effects of structural violence that disproportionately afflict AA individuals may influence tumor biology and outcomes. We previously reported differentially expressed genes (DEGs) associated with tumor aggressiveness in Basal tumors from AA compared with NHW (Sharma et al., 2020). Here, we compare DEGs in luminal tumors between AA and NHW. Methods: The prospective, observational FLEX study (NCT03053193) includes stage I-III breast cancer patients who receive 70-gene signature (MammaPrint/MP)/80-gene signature (BluePrint/BP) testing and consent to full transcriptome and clinical data collection. AA (n=364) and NHW (n=400, random selection) with BP luminal tumors, enrolled from 2017 to present, were included. Race/ethnicity was self-reported. AA were younger than NHW (mean, 59 vs. 62 years, p=0.001); thus, an age-matched subset (n= 360 AA, NHW) was compared. Differential gene expression analysis was performed with R limma package. Comparisons were made between AA and age-matched or randomly selected NHW in: (1) all, (2) luminal A, (3) luminal B, and (4) luminal B, obese. DEGs with FDR<0.05 were significant. Different fold change (FC) thresholds were evaluated. Results: Compared with age-matched NHW, AA were similar in menopausal status, T stage, grade, and tumor type; obesity, T2DM status, and nodal stage were significantly different ( p<0.01). Tumors from AA were more often MP high risk ( p<0.001), regardless of age matching. Luminal B AA vs. age-matched NHW comparison resulted in more DEGs (n=1070) than other comparisons; however, most were FC<2. Notably, 5/6 DEGs ( PSPH, NOTCH2NL, POLR1A, MAP1LC3P and RPS26P10) in basal tumors (Nunes et al. 2019) were also identified here. Of 9 DEGs (FC>1.7) in the luminal B age-matched comparison, 2 ( PSPH and LINC01139) were also found in the luminal B, obese subset. Consistently upregulated DEGs in AA were associated with metabolism, translation, and cellular stress response pathways. Conclusions: We found significant transcriptomic differences between luminal tumors from AA and NHW, when controlling for age, obesity, and genomic classification. A subset of DEGs in luminal B tumors were consistent with those in Basal tumors, suggesting that similar race-associated factors drive DEGs regardless of tumor subtype. DEGs that may be unique to AA luminal tumors were also found. This study suggests that some biological differences in breast tumors may result from patient ancestry or shared adverse socioeconomic exposures and underscores the need for inclusion of diverse patient groups in clinical trials. Clinical trial information: NCT03053193.