Abstract 1176: Racial differences in circulating inflammatory cytokines and breast cancer disparities
Authors: Danciu Oana C. , Chlipala George , Madak-Erdogan Zeynep , Patel Hariyali , Banks Landan , Zaidi Ayesha , Santaliz-Casiano Ashlie , Schulte Lauren , Weller Lauren , Taiym Deanna , Pulliam Natalie , Hazizi Elona Liko , Martin Elonia , Fareeduddin Anita , Bargaje Archana , Garcia Carlos , Hegerty Scott , Friedewald Sarah , Khan Seema , Kim J Julie , Gradishar William , Rauscher Garth , Frasor Jonna , Hoskins Kent F. 
Published: September 2020

Introduction

Racial disparities in breast cancer (BrCa) mortality are well documented. We previously reported that African American (AA) women with estrogen receptor-positive (ER+) BrCa have a 4-fold higher rate of death compared to non-Hispanic whites (white) after controlling for stage at diagnosis and treatment initiation. This suggests that racial differences in tumor biology may contribute to the survival disparity. In preliminary work we found that AA BrCa cases have higher serum levels of C-reactive protein (CRP) compared to whites, and that increased CRP was associated with worse survival, suggesting that increased systemic inflammation in AA women drives aggressive tumor biology and contributes to the racial disparity in survival. The goal of this study is to identify specific inflammatory pathways that may be involved.

Experimental Procedures

Pre-treatment blood samples from women with stage I-III ER+ BrCa (AA, n=40; white, n=55) and from healthy controls (AA, n=51; white, n=38) were analyzed with the Olink® targeted proteomic assay, which measures 92 inflammatory proteins. Normalized data was log2 transformed, and generalized linear models compared the normalized intensities with covariates of interest. The fit of the model was tested with empirical Bayes methods. All p-values are corrected for multiple testing with the false discovery rate (FDR) method of Benjamini and Hochberg.

Findings

After adjustment for site of enrollment, plasma levels of 13 inflammatory cytokines showed a log2 fold-change (log2FC) ≥ 1.0 for AA compared to white women, i.e. at least a two-fold increase in the mean value on a linear scale (Table). The racial difference was evident among both cases and controls, and remained after adjusting for body mass index (BMI). There were no differences between AA cases and controls, indicating that cytokine elevation in AA BrCa patients is not an effect of the tumor. Several of the cytokines are known to promote tumor progression and aggressive biological features in breast tumors.

ProteinLog2FCProteinLog2FCCXCL52.42**CCL81.13***CXCL12.06***EIF4EBP11.12**STAMBP1.91*CCL201.10**CXCL111.89**TNF141.06*CCL31.45**TGF beta1.04**CXCL61.40**CCL71.03***CCL131.16**FDR corrected p-values: * &lt; 0.05, **&lt; 0.01, ***&lt; 0.001

Conclusion

Systemic elevation of biologically relevant inflammatory cytokines in AA women with ER+ BrCa does not appear to be an effect of the tumor. This inflammatory phenotype may activate inflammatory programs in ER+ breast tumors that develop in AA women, leading to disproportionately aggressive tumor biology and worse outcomes.

Supported by grants U54CA203000; U54CA2022995; and U54CA2022997 from the National Institutes of Health.

Citation Format: Oana C. Danciu, George Chlipala, Zeynep Madak-Erdogan, Hariyali Patel, Landan Banks, Ayesha Zaidi, Ashlie Santaliz-Casiano, Lauren Schulte, Lauren Weller, Deanna Taiym, Natalie Pulliam, Elona Liko Hazizi, Elonia Martin, Anita Fareeduddin, Archana Bargaje, Carlos Garcia, Scott Hegerty, Sarah Friedewald, Seema Khan, J Julie Kim, William Gradishar, Garth Rauscher, Jonna Frasor, Kent F. Hoskins. Racial differences in circulating inflammatory cytokines and breast cancer disparities [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1176.