Prediction of Specific Survival and Clinicopathological Impact of Somatic PALB2 Mutations and Pathogenic/Likely Pathogenic Variants (PV/LPV) in Breast Cancer: A Cohort Study of 81 Patients

<i>PALB2</i> plays a crucial role in DNA repair by interacting with <i>BRCA1</i> and <i>BRCA2</i>. To clarify the clinicopathological impact of somatic PALB2 variants, we analyzed tumor DNA extracted from formalin-fixed, paraffin-embedded (FFPE) breast cancer specimens from 81 patients. Targeted next-generation sequencing identified 1 514 variants, including 84 pathogenic or likely pathogenic variants and 9 genes with high mutation frequency; 2 deleterious somatic <i>PALB2</i> variants were detected in 33% of samples. To explore transcriptional effects, we analyzed publicly available METABRIC mRNA expression data and found that elevated <i>PALB2</i> mRNA levels were significantly associated with ER-/PR- tumors and poorer survival outcomes. High <i>PALB2</i> expression remained an independent predictor of shorter overall survival and relapse-free survival. These findings highlight the clinical importance of somatic <i>PALB2</i> mutations and the prognostic value of <i>PALB2</i> expression in breast cancer.