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Background <p>Estrogen receptor (ER) expression in breast cancer exhibits a widely recognized bimodal distribution, with increasing focus on the biological and clinical characteristics of the low-expression group. However, tumors with intermediate ER expression have been relatively understudied. This study aimed to clarify the clinicopathological and prognostic features of ER-intermediate (ER-int) tumors by comparing them with ER-low tumors.</p> Methods <p>Tumors were classified into ER-low (1–10%), ER-int (11–70%), and ER-high (71–100%) groups based on immunohistochemistry. We retrospectively analyzed 261 breast cancer patients with ER-low or ER-int tumors who underwent curative surgery. Clinicopathological features and treatment outcomes were compared, and factors influencing distant recurrence-free survival (DRFS) and overall survival (OS) were evaluated using Cox proportional hazard models. For analysis of clinical outcomes, after excluding HER2-positive tumors, an additional cohort of 604 patients with ER-high and HER2-negative tumors was also compared.</p> Results <p>ER-int tumors showed lower nuclear grade, higher progesterone receptor expression, and lower Ki67 labeling index compared with ER-low tumors. Pathological stage was independently associated with both DRFS and OS. In addition, ER status was also an independent factor for OS, with ER-int tumors showing significantly better OS than ER-low tumors (P = 0.014).</p> Conclusions <p>Our findings, based on comparison with ER-low tumors, suggest that intermediate ER expression may represent a biologically and clinically heterogeneous subgroup within ER-positive breast cancers. Recognition of this heterogeneity could help refine classification and support more individualized treatment strategies.</p>

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Breast tumors with intermediate ER expression differ biologically from ER-low tumors and exhibit a more favorable prognosis

  • 期刊论文

  • 发表日期：

    2025年7月20日

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  • Yuko Ueki,
  • Yoshiya Horimoto,
  • Kazuharu Harada,
  • Yumiko Ushiyama,
  • Yumiko Ishizuka,
  • Hiroko Onagi,
  • Takuo Hayashi,
  • Tsuyoshi Saito,
  • Takahiko Kawate,
  • Takashi Ishikawa,
  • Junichiro Watanabe,
  • Goro Kutomi

摘要

Background

Estrogen receptor (ER) expression in breast cancer exhibits a widely recognized bimodal distribution, with increasing focus on the biological and clinical characteristics of the low-expression group. However, tumors with intermediate ER expression have been relatively understudied. This study aimed to clarify the clinicopathological and prognostic features of ER-intermediate (ER-int) tumors by comparing them with ER-low tumors.

Methods

Tumors were classified into ER-low (1–10%), ER-int (11–70%), and ER-high (71–100%) groups based on immunohistochemistry. We retrospectively analyzed 261 breast cancer patients with ER-low or ER-int tumors who underwent curative surgery. Clinicopathological features and treatment outcomes were compared, and factors influencing distant recurrence-free survival (DRFS) and overall survival (OS) were evaluated using Cox proportional hazard models. For analysis of clinical outcomes, after excluding HER2-positive tumors, an additional cohort of 604 patients with ER-high and HER2-negative tumors was also compared.

Results

ER-int tumors showed lower nuclear grade, higher progesterone receptor expression, and lower Ki67 labeling index compared with ER-low tumors. Pathological stage was independently associated with both DRFS and OS. In addition, ER status was also an independent factor for OS, with ER-int tumors showing significantly better OS than ER-low tumors (P = 0.014).

Conclusions

Our findings, based on comparison with ER-low tumors, suggest that intermediate ER expression may represent a biologically and clinically heterogeneous subgroup within ER-positive breast cancers. Recognition of this heterogeneity could help refine classification and support more individualized treatment strategies.