IMMUNE RICH TRIPLE NEGATIVE BREAST CANCER

In a study reported in JAMA Oncology, Karn et al found that triple-negative breast cancers with high immune gene expression levels were characterized by lower clonal heterogeneity, reduced copy number alterations, and lower somatic mutation and neoantigen loads.

Study Details

In the study, DNA and RNA sequencing and messenger RNA expression data from The Cancer Genome Atlas breast cancer data set were used to calculate immune metagene expression values and histologic lymphocyte counts to measure immune infiltration and determine prognostic categories of triple-negative breast cancers. Among 193 triple-negative breast cancer samples with survival information, 25 were classified as good prognosis, defined as high immune infiltration (ie, major histocompatibility complex class II metagene expression in the top quartile) and low inflammation markers (ie, interleukin 8–vascular endothelial growth factor metagene expression below the median). Disease-free survival was significantly better in the good-prognosis group (P = .02). Immune-rich good prognosis and immune-poor poor prognosis cohorts were compared for clonal heterogeneity, somatic total mutational load, neoantigen load, and somatic copy number alteration levels.

Immune Infiltration and Tumor Characteristics

The immune-rich good prognosis samples had significantly lower mutant-allele tumor heterogeneity (MATH) scores, indicating lower clonal genomic heterogeneity (P = .001). Among all tumors, there were inverse associations between clonal heterogeneity and immune metagene expression (ρ = −0.395, P = 2 × 10−8), particularly marked in good-prognosis triple-negative breast cancers, and between somatic copy number alteration levels and immune metagene expression (ρ = −0.484, P = 2 × 10−10). Levels of somatic copy number alterations were significantly lower in good-prognosis triple-negative breast cancers (P < .001), as were somatic mutational load (P = .02) and neoantigen load (P = .04), compared with poor-prognosis triple-negative breast cancers. Findings were confirmed in an independent data set (METABRIC).

The investigators 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. These cancers may also represent the subset of [triple-negative breast cancers] that could derive benefit from immune checkpoint inhibitor therapy to tilt the balance in favor of the immune system.”

The study was supported by H.W. & J. Hector-Stiftung, the Breast Cancer Research Foundation, the Susan Komen Foundation, the National Cancer Institute, and Associazione Italiana per la Ricerca sul Cancro.