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Background <p>Estrogen receptor (ER) expression is critical in breast cancer treatment. While low ER (1–9%) resembles triple-negative cancer with chemotherapy efficacy, the significance of “intermediate expression” (≥ 10%) and the therapeutic efficacy remain unclear. This study explores the differences in staining patterns and molecular characteristics of ER-low to intermediate expression to guide treatment.</p> Methods <p>A total of 104 breast cancer patients treated between January 2008 and July 2024 with an Allred Proportion Score (PS) of 2–4 were included. PS2 (<i>n</i> = 21) was classified as ER-low, while PS3 (<i>n</i> = 26) and PS4 (<i>n</i> = 57) as ER-intermediate (ER-int). ER-int was further divided by ER staining pattern: “Island” (heterogeneous) and “Scatter,” (uniform) subgroups. The prognosis, clinical factors, and gene expression profiles (<i>n</i> = 11) were analyzed.</p> Results <p>The Island subgroup was associated with poorest prognosis (<i>p</i> = 0.0116), particularly among the patients treated with endocrine-only treatment patients (<i>p</i> &lt; 0.0001). Elevated tumor-infiltrating lymphocyte (TIL) levels correlated with worse prognosis in endocrine-only treatment patients (<i>p</i> &lt; 0.0043), with TIL levels highest in ER-low, followed by Island and Scatter subgroups. Island tumors were enriched in CD36, GZMB, and type I interferon genes; additionally, 23 “ISLAND” genes showed significant prognostic differences in the TCGA BRCA ER-int (10–69%) cohort.</p> Conclusion <p>This study emphasizes the importance of recognizing heterogeneity within the ER-int subtype. Identifying distinct ER staining patterns and prognostic significance of TILs and transcriptome in ER-int tumors suggests the need for individualized treatment strategies for Island subtype.</p>

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Prognostic impact of ER-staining patterns and heterogeneity of ER positive HER2 negative breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月18日

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  • Yumiko Akita,
  • Ravi Velaga,
  • Madoka Iwase,
  • Satoko Shimada,
  • Toyone Kikumori,
  • Dai Takeuchi,
  • Yuko Takano,
  • Takahiro Ichikawa,
  • Tomoki Ebata,
  • Norikazu Masuda

摘要

Background

Estrogen receptor (ER) expression is critical in breast cancer treatment. While low ER (1–9%) resembles triple-negative cancer with chemotherapy efficacy, the significance of “intermediate expression” (≥ 10%) and the therapeutic efficacy remain unclear. This study explores the differences in staining patterns and molecular characteristics of ER-low to intermediate expression to guide treatment.

Methods

A total of 104 breast cancer patients treated between January 2008 and July 2024 with an Allred Proportion Score (PS) of 2–4 were included. PS2 (n = 21) was classified as ER-low, while PS3 (n = 26) and PS4 (n = 57) as ER-intermediate (ER-int). ER-int was further divided by ER staining pattern: “Island” (heterogeneous) and “Scatter,” (uniform) subgroups. The prognosis, clinical factors, and gene expression profiles (n = 11) were analyzed.

Results

The Island subgroup was associated with poorest prognosis (p = 0.0116), particularly among the patients treated with endocrine-only treatment patients (p < 0.0001). Elevated tumor-infiltrating lymphocyte (TIL) levels correlated with worse prognosis in endocrine-only treatment patients (p < 0.0043), with TIL levels highest in ER-low, followed by Island and Scatter subgroups. Island tumors were enriched in CD36, GZMB, and type I interferon genes; additionally, 23 “ISLAND” genes showed significant prognostic differences in the TCGA BRCA ER-int (10–69%) cohort.

Conclusion

This study emphasizes the importance of recognizing heterogeneity within the ER-int subtype. Identifying distinct ER staining patterns and prognostic significance of TILs and transcriptome in ER-int tumors suggests the need for individualized treatment strategies for Island subtype.