Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a dNTP hydrolase important for intracellular dNTP homeostasis and serves as tumor suppressor and modulator of antimetabolite efficacy in cancer, though largely unexplored in breast cancer (BC). A cohort of patients with early BC (n = 564) with available gene expression data (GEP) was used. SAMHD1 protein expression was assessed by immunohistochemistry performed on tissue microarrays. A large pooled transcriptomic dataset was used for validation (n = 2402). GEP data from the metastatic TEX randomized phase III trial (NCT01433614) were used for SAMHD1 predictive evaluation in response to capecitabine. SAMHD1 protein and mRNA levels were higher in HER2-enriched/HER2+ and basal-like (BL)/ER-/HER2- BC. Both SAMHD1 gene and protein expression were independently associated with favorable outcomes in BL tumors. In the pooled dataset, SAMHD1 gene expression was independently associated with favorable disease-free survival in the entire population and within the BL and HER2-enriched molecular subtypes. In metastatic BC, SAMHD1 mRNA levels were higher in responders receiving capecitabine. In conclusion SAMHD1 gene and protein expression represent promising prognostic biomarkers in BL early BC.
Keywords: SAMHD1; STING; basal‐like; biomarker; breast cancer; prognosis.
© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.