Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival.
Clin Cancer Res
; 26(8): 1905-1914, 2020 04 15.
Article
in En
| MEDLINE
| ID: mdl-31911546
ABSTRACT
PURPOSE:
Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor-positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation. EXPERIMENTALDESIGN:
Data and biospecimens from 262 AA and 293 EA patients diagnosed with breast cancer from 2001 to 2010 at a major medical center were analyzed by IHC for functional biomarkers of luminal differentiation, including estrogen receptor (ESR1) and its pioneer factors, FOXA1 and GATA3. Integrated comparison of protein levels with network-level gene expression analysis uncovered predictive correlations with race and survival.RESULTS:
Univariate or multivariate HRs for overall survival, estimated from digital IHC scoring of nuclear antigen, show distinct differences in the magnitude and significance of these biomarkers to predict survival based on race ESR1 [EA HR = 0.47; 95% confidence interval (CI), 0.31-0.72 and AA HR = 0.77; 95% CI, 0.48-1.18]; FOXA1 (EA HR = 0.38; 95% CI, 0.23-0.63 and AA HR = 0.53; 95% CI, 0.31-0.88), and GATA3 (EA HR = 0.36; 95% CI, 0.23-0.56; AA HR = 0.57; CI, 0.56-1.4). In addition, we identify genes in the downstream regulons of these biomarkers highly correlated with race and survival.CONCLUSIONS:
Even within clinically homogeneous tumor groups, regulatory networks that drive mammary luminal differentiation reveal race-specific differences in their association with clinical outcome. Understanding these biomarkers and their downstream regulons will elucidate the intrinsic mechanisms that drive racial disparities in breast cancer survival.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Black People
/
White People
/
Estrogen Receptor alpha
/
GATA3 Transcription Factor
/
Hepatocyte Nuclear Factor 3-alpha
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Middle aged
Country/Region as subject:
America do norte
Language:
En
Journal:
Clin Cancer Res
Journal subject:
NEOPLASIAS
Year:
2020
Type:
Article