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

Yuko Ueki ¹, Yoshiya Horimoto ^2,3,4, Kazuharu Harada ⁵

⁰Department of Breast Oncology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Cancer +

|

July 20, 2025

View abstract on PubMed

Summary

Intermediate estrogen receptor (ER) expression in breast cancer is distinct from ER-low tumors, showing better overall survival. This finding highlights the heterogeneity within ER-positive breast cancers, suggesting tailored treatment approaches.

Area Of Science

Oncology
Breast Cancer Research
Molecular Pathology

Background

Estrogen receptor (ER) expression in breast cancer typically shows a bimodal distribution.
ER-low tumors are increasingly studied, but ER-intermediate tumors remain under-investigated.
Understanding ER-intermediate tumors is crucial for refining breast cancer classification.

Purpose Of The Study

To investigate the clinicopathological and prognostic features of ER-intermediate (ER-int) breast tumors.
To compare ER-int tumors with ER-low tumors.
To identify factors influencing distant recurrence-free survival (DRFS) and overall survival (OS).

Main Methods

Retrospective analysis of 261 breast cancer patients with ER-low or ER-int tumors.
Tumor classification based on immunohistochemistry: ER-low (1-10%), ER-int (11-70%), ER-high (71-100%).
Cox proportional hazard models used to evaluate survival outcomes; comparison cohort included ER-high, HER2-negative tumors.

Main Results

ER-int tumors exhibited lower nuclear grade, higher progesterone receptor expression, and lower Ki67 index than ER-low tumors.
Pathological stage was an independent predictor for both DRFS and OS.
ER-int tumors demonstrated significantly better OS compared to ER-low tumors (P=0.014).

Conclusions

Intermediate ER expression defines a biologically and clinically heterogeneous subgroup within ER-positive breast cancers.
ER-int tumors possess distinct characteristics compared to ER-low tumors.
Recognizing this heterogeneity can lead to improved classification and personalized treatment strategies for breast cancer.

Keywords:

Breast neoplasms Chemotherapy Estrogen receptor alpha Hormone-dependent neoplasms Immunohistochemistry Prognostic factor

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