Racial and Ethnic Differences in Drug Disposition and Response: Review of New Molecular Entities Approved Between 2014 and 2019.

Race and ethnicity can contribute to differences in drug exposure and/or response. Here, we report that about 10% of the new molecular entities (NMEs) approved between 2014 and 2019 by the US Food and Drug Administration's Center for Drug Evaluation and Research showed differences in exposure and/or response based on race/ethnicity or pharmacogenetic factors known to vary in frequency across global populations. Fewer NMEs (10%) reported differences in the labeling in 2014 to 2019 when compared to about 21% of NMEs approved between 2008 and 2013 that had differences in pharmacokinetics, safety, response, and/or pharmacogenetics. Understanding the underlying mechanisms that lead to such differences and adequate enrollment of racial and ethnic subgroups is essential to obtain sufficient information on exposure and response. Though drug development is global, when heterogeneous populations are not adequately enrolled, the risk-benefit assessments can remain incomplete for certain subgroups. Consequently, this can result in regional differences in drug approval, population-specific prescribing recommendations, or need for additional postmarketing studies to address concerns related to exposure, response, or lack of representation that lead to gaps in information.

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

BACKGROUND: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. METHOD: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. RESULTS: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. CONCLUSION: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Hepatitis C Among High-Risk Alabamians: Disease Burden and Screening Effectiveness.

BACKGROUND: The effectiveness of hepatitis C testing and linkage-to-care (LTC) is poorly characterized in low-resource jurisdictions facing gaps in harm reduction, including illegality of syringe exchange services. Effectiveness of a community-based test/LTC program was evaluated in Alabama. METHODS: In 2016-2018, shelters, drug treatment centers (DTCs), AIDS organizations, and Federally Qualified Health Centers (FQHCs) engaged in screening/LTC. A coordinator navigated individuals to confirm viremia and link to substance use treatment or primary care with hepatitis C prescribers. RESULTS: Point-of-care (POC) tested 4293 individuals (10% [427] antibody-positive, 71% [299/419] RNA performed, 80% [241/299] viremia confirmed) and 93% linked to care (225/241). Electronic medical record (EMR)-based reflex strategy screened 4654 (15% [679] antibody positive, 99% [670/679] RNA performed, 64% [433/679] viremia confirmed) and 85% linked to care (368/433). We observed higher odds of RNA confirmation in EMR-based reflex versus POC (OR, 2.07; P < .0001) and higher odds of LTC in EMR-based reflex versus POC (OR, 1.51; P < .0001). Overall, 53% individuals tested were nonbaby boomers. CONCLUSIONS: In Alabama, screening at high-risk settings identified significant hepatitis C burden and reflex testing outperformed point-of-care linkage indicators. Colocating testing in DTCs and treatment in FQHCs provided key LTC venues to at-risk younger groups.