Racial differences in genomic profiles and targeted treatment use in ER+ HER2- metastatic breast cancer.
Authors: Podany Emily L. , Foffano Lorenzo , Gerratana Lorenzo , Medford Arielle J , Clifton Katherine , Tapiavala Shaili , Velimirovic Marko , Lipsyc-Sharf Marla , Shah Ami N. , Reduzzi Carolina , Munoz-Arcos Laura Sofia , Putur Annika , Ademuyiwa Foluso Olabisi , Puglisi Fabio , Ma Cynthia X. , Bardia Aditya , Cristofanilli Massimo , Davis Andrew A. 
Published: June 2024

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Background: Despite well-documented disparities in survival between patients (pts) with Black and White racial backgrounds, there are limited data on racial equity of targeted treatment use for pts with estrogen receptor positive, HER2 negative (ER+/HER2-) metastatic breast cancer (MBC). We evaluated differences in circulating tumor DNA (ctDNA) genomic alterations in Black and White pts with ER+/HER2- MBC. Methods: This retrospective cohort study analyzed a database of 1327 pts with MBC who were treated at Washington University in St. Louis, Massachusetts General Hospital, and Northwestern University and had ctDNA testing through the commercially available Guardant360 assay. Progesterone receptor (PR) status of the ER+/HER2- pts was identified to categorize pts as ER+/PR+/HER2- (N=60 Black, N=435 White) and ER+/PR-/HER2- (N=24 Black, N=237 White). Pts were evaluated by self-reported race and use of PIK3CA, CDK4/6, and mTOR inhibitors, either through clinical trial enrollment or after FDA approval. A multivariate logistic analysis was performed to determine genomic and prognostic differences by race. Overall survival (OS) from time of first ctDNA testing was determined by subgroup. Results: Black pts with PIK3CA single nucleotide variants (SNVs) were significantly less likely to receive targeted therapy than White pts (5.9%, 1/17 pts vs. 28.8%, 45/156 pts, Fisher’s exact test p=0.045), while there was no difference in use of CDK4/6 or mTOR inhibitors. None of the Black pts with PIK3CA mutations were enrolled in clinical trials vs. 11.5% of White pts. Black pts with ER+/PR+/HER2- tumors were more likely to have CCND1 copy number variation (cnv) (odds ratio (OR) 2.4, 95% confidence interval (CI) 1.1-5.4, p=0.030) when compared with White pts. Black pts with PR- tumors were more likely to have de novo metastatic disease (OR 3.4, 95% CI 1.1-10.8, p=0.034) and GATA3SNV (OR 3.5, 95% CI 1.04-11.6, p=0.044). KRAS cnv was more common in White PR- pts (HR 2.9, CI 1.02-8.3, p=0.045). There were significant differences in OS between Black and White pts with ER+/PR+/HER2- tumors (median OS of 25 vs. 32 months, respectively) and for Black and White pts with ER+/PR-/HER2- MBC, (median OS of 9.1 vs. 21 months, respectively, log-rank test p=0.00093). Conclusions: To our knowledge, this is the largest clinicogenomic dataset comparing genomic alterations and targeted treatment use by race in MBC. We identified significant disparities in the use of PI3K inhibitors for Black pts while other drugs that do not require genomic profiling were similarly utilized. OS and clinical trial enrollment disparities are consistent with prior findings and must continue to be addressed. Further research is needed to validate these findings, elucidate the factors contributing to these disparities, and explore interventions to improve racial disparities in use of precision medicine therapies and enrollment in clinical trials.