Key Findings
- This large cohort revealed meaningful discordance between PTEN protein loss by IHC and PTEN genomic alterations by NGS in HR+/HER2– metastatic breast cancer.
- The discordant subsets showed distinct co-occurrence patterns with PIK3CA and AKT1 mutations, and PTEN IHC identified additional tumors with apparent PI3K/AKT activation that would not be detected by NGS alone.
- These findings support a multimodal testing approach and suggest that PTEN IHC may capture additional patients with pathway activation relevant to treatment resistance and therapeutic selection.