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Background <p>Estrogen receptor alpha (ESR1) mutations represent a critical mechanism of endocrine resistance in hormone receptor-positive (HR+) breast cancer, affecting 10–55% of metastatic cases. The relationship between ESR1 mutations and programmed death-ligand 1 (PD-L1) expression remains poorly understood, with potential implications for immunotherapy selection and combination strategies.</p> Objective <p>To systematically review and meta-analyze the correlation between ESR1 mutations and PD-L1 expression in HR + breast cancer, examining the underlying mechanisms and clinical implications.</p> Methods <p>We conducted a comprehensive systematic literature search of PubMed, EMBASE, and Cochrane databases from January 2015 to September 2025. Studies investigating ESR1 mutations, PD-L1 expression, and immune microenvironment characteristics in HR + breast cancer were included. Data extraction focused on mutation prevalence, PD-L1 expression patterns, immune infiltration levels, and mechanistic insights.</p> Results <p>Twelve studies comprising 2,089 patients with HR + breast cancer were included in the final analysis. ESR1 mutations showed a complex, stage-dependent relationship with PD-L1 expression and immune activation. In primary tumors, ESR1 mutations were associated with increased basal-like features and enhanced immune activation signatures. However, in advanced metastatic disease, ESR1 mutations correlated with immune escape mechanisms, including significant downregulation of HLA class I (<i>p</i> &lt; 0.001) and class II molecules, reduced CD8 + T cell infiltration, and decreased PD-L1 expression in tumor-infiltrating immune cells.</p> Conclusions <p>The ESR1 mutation-PD-L1 relationship exhibits temporal and contextual complexity, with potential immunostimulatory effects in early disease transitioning to immune-suppressive phenotypes in advanced stages. These findings have important implications for immunotherapy timing and combination strategies in ESR1-mutated HR + breast cancer.</p>

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ESR1 mutations and PD-L1 expression in hormone receptor-positive breast cancer: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月23日

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  • Kartavya Kumar Verma

摘要

Background

Estrogen receptor alpha (ESR1) mutations represent a critical mechanism of endocrine resistance in hormone receptor-positive (HR+) breast cancer, affecting 10–55% of metastatic cases. The relationship between ESR1 mutations and programmed death-ligand 1 (PD-L1) expression remains poorly understood, with potential implications for immunotherapy selection and combination strategies.

Objective

To systematically review and meta-analyze the correlation between ESR1 mutations and PD-L1 expression in HR + breast cancer, examining the underlying mechanisms and clinical implications.

Methods

We conducted a comprehensive systematic literature search of PubMed, EMBASE, and Cochrane databases from January 2015 to September 2025. Studies investigating ESR1 mutations, PD-L1 expression, and immune microenvironment characteristics in HR + breast cancer were included. Data extraction focused on mutation prevalence, PD-L1 expression patterns, immune infiltration levels, and mechanistic insights.

Results

Twelve studies comprising 2,089 patients with HR + breast cancer were included in the final analysis. ESR1 mutations showed a complex, stage-dependent relationship with PD-L1 expression and immune activation. In primary tumors, ESR1 mutations were associated with increased basal-like features and enhanced immune activation signatures. However, in advanced metastatic disease, ESR1 mutations correlated with immune escape mechanisms, including significant downregulation of HLA class I (p < 0.001) and class II molecules, reduced CD8 + T cell infiltration, and decreased PD-L1 expression in tumor-infiltrating immune cells.

Conclusions

The ESR1 mutation-PD-L1 relationship exhibits temporal and contextual complexity, with potential immunostimulatory effects in early disease transitioning to immune-suppressive phenotypes in advanced stages. These findings have important implications for immunotherapy timing and combination strategies in ESR1-mutated HR + breast cancer.