# Hormone Receptor Positive/HER2 Negative Breast Carcinoma: Association of PIK3CA Mutational Status with PD-L1 and Tumor Cell Microenvironment and Their Prognostic Significance

## TL;DR

This study explores how PIK3CA mutations in certain breast cancers are linked to immune markers like PD-L1 and immune cell infiltration, and how these factors may affect patient survival.

## Contribution

The study identifies a novel association between PIK3CA mutations and immune markers in HR+/HER2− breast cancer, suggesting potential implications for treatment strategies.

## Key findings

- PIK3CA exon 20 mutations are significantly associated with PD-L1 expression in HR+/HER2− breast cancer.
- Tumors with PIK3CA mutations show strong correlations between PD-L1 and immune cell infiltration (CD8, CD68, CD163).
- Patients with PIK3CA mutations, especially exon 20 mutations, have significantly longer survival without recurrence.

## Abstract

Novel research data in different cancer types indicate that mutations within PIK3CA might serve as a biomarker of an improved response to immune therapy. Therefore, the aim of this study was to evaluate and examine possible differences in the tumor microenvironment composition and PD-L1 expression as well the prognostic significance of CD4, CD8, CD68, and CD163 in PIK3CA mutated and non-mutated hormone receptor positive and HER2 negative (HR+/HER2−) breast carcinoma. Breast carcinoma tissue was analyzed by Cobas PIK3CA mutation test for the presence of PIK3CA mutation and immunohistochemistry was applied to assess PD-L1 expression and CD4, CD8, CD68, and CD163 infiltration within tumor. Statistically significant association was observed between PD-L1 expression and the presence of PIK3CA exon 20 mutation (p = 0.044), with PD-L1–positive patients predominantly harboring this mutation. Tumors harboring PIK3CA mutations exhibited moderate to strong statistically significant positive correlations between PD-L1 expression and infiltration by CD8 cells (rs = 0.462, p = 0.0027), CD68 cells (rs = 0.398, p = 0.0134), and CD163 cells (rs = 0.617, p < 0.0001). In patients with PIK3CA mutation and exon 20 PIK3CA mutation there was statistically significant longer survival without recurrence (p = 0.026 and p = 0.041, respectively). Research regarding PD-L1 expression, immune cells and PIK3CA mutations might have an impact on how to determine therapeutic approaches for patients with HR+/HER2− breast carcinoma.