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Triple-Negative Breast Cancer: Genomic Metrics and Immune Infiltration

Understanding how immune surveillance shapes the cancer genome may help clinicians to select patients who could derive benefit from immune checkpoint inhibitor therapy, according to Thomas Karn, PhD, of Goethe-University Frankfurt, Germany, and colleagues. The findings of their study, which examined the association between genomic metrics and the extent of immune infiltration in triple-negative breast cancers, were published in JAMA Oncology.

Using DNA and RNA sequencing data and messenger RNA expression results from The Cancer Genome Atlas breast cancer data set, the investigators identified 193 triple-negative breast cancer samples with survival information; 25 were classified as having a good prognosis, which was defined as high immune infiltration and low inflammation markers.

An inverse association between clonal heterogeneity and immune metagene expression—as well as between immune metagene expression and somatic copy number alteration levels—was found. Triple-negative breast cancers with high immune gene expression had lower clonal heterogeneity, fewer copy number alterations, lower somatic mutation, and lower neoantigen loads.

Dr. Karn and colleagues concluded: “This study suggests that immune-rich [triple-negative breast cancers] may be under an immune surveillance that continuously eliminates many immunogenic clones, resulting in lower clonal heterogeneity.” Immune checkpoint inhibitor therapy may prove to be of benefit to patients with this subset of triple-negative breast cancers.



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