MYC is one of the most studied oncogenes that is known to promote cell proliferation. We utilized MYC targets v1 and MYC targets v2 scores of gene set variation analysis and hypothesized that these scores correlate with tumor aggressiveness and survival outcomes. We examined a total of 3109 breast cancer patients from TCGA, METABRIC, and GSE124647 cohorts. In each cohort, the patients were divided into high- and low-score groups using the upper third value as the cut off. As expected, higher

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... res were related to increased cell proliferation and worse clinical and pathologic features. High MYC targets scores were associated with worse survival, specifically in primary ER-positive breast cancer, consistently in both TCGA and METABRIC cohorts. In ER-positive breast cancer, high MYC targets v1, but not v2 score, was associated with high mutation load, and high MYC targets v1 and v2 scores were both associated with increased infiltration of pro- and anti-cancerous immune cells. We found that high MYC scores were associated with worse survival in metastatic breast cancer. Our findings show that the MYC targets v1 and v2 scores are associated with tumor aggressiveness and poor prognosis in ER-positive primary tumors, as well as in metastatic breast cancer.