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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Tuesday, April 9, 2024
Using cellular heterogeneity to determine the specific subtype of triple-negative breast cancer may be a novel mechanism to further classify patients, according to a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract LB006/6). This approach may improve clinical outcomes for this patient population by employing subtype-specific treatment strategies, suggested Shankar Subramaniam, PhD, of the University of California San Diego, La Jolla, and colleagues.
The study encompassed a total of 250 European (n = 114) and African (n = 136) women with triple-negative breast cancer. RNA-sequencing data were collected from these patients and analyzed for the expression of 261 different breast-specific cell-type markers. Differentially expressed genes, protein-protein interactions, and genes regulated by transcription factors were employed to establish endotype-specific networks.
The analysis revealed pronounced heterogeneity across three distinct mechanistic subtypes (CC1-3) in patients with triple-negative breast cancer. Each of these subtypes contained nine distinct groups labeled HC1-9. In addition, an array of unique biomarkers was identified within each subtype, suggesting increased diversity among adipogenesis, extracellular matrix, immune, and inflammatory signatures. Patients with the CC1 mechanistic subtype demonstrated an upregulation of interferon and interleukin markers and CD8 T-cell activation, whereas patients with the CC2 subtype showed an upregulation of extracellular matrix genes. Furthermore, patients with the CC3 subtype demonstrated an upregulation of genes associated with hormone sensitivity, fatty acid regulation, and inflammation. Moreover, self-reported race-inferred prognostic biomarkers were identified in the CC2 subtype and included ANKRD30A, KRT86, and TTC6.
Disclosure: The study authors reported no conflicts of interest.
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