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. 2021 Jul;188(1):225-235.
doi: 10.1007/s10549-021-06148-0. Epub 2021 Mar 10.

Characterization of estrogen receptor-low-positive breast cancer

Fei Fei  1 , Gene P Siegal  1   2 , Shi Wei  3   4
Affiliations

Characterization of estrogen receptor-low-positive breast cancer

Fei Fei et al. Breast Cancer Res Treat. 2021 Jul.

Abstract

Purpose: The biology of breast cancer with a low expression level (1-10%) of estrogen receptor (ER) remains a matter of confusion. The recent American Society of Oncology/College of American Pathologist Guidelines have recommended reporting such tumors as a new "ER-low-positive" category with a recommended comment to emphasize the possible overall benefit of endocrine therapies in these patients. The aim of the study was to analyze the clinicopathologic features and clinical outcomes of ER-low-positive breast cancers.

Methods: We characterized the clinicopathologic features and survival outcomes of ER-low-positive breast cancers in our 4179 patients diagnosed from 1998 to 2018.

Results: The ER-positive, ER-low-positive, and ER-negative cases in our cohort were 2982 (71.4%), 97 (2.3%), and 1100 (26.3%), respectively. ER-low-positive tumors showed similar clinicopathologic characteristics yet significantly superior prognosis when compared to ER-negative tumors, while demonstrated largely overlapping survival outcomes with ER-positive tumors in the entire cohort. In the subcohort of tumors with a PR-positive phenotype, the prognosis of ER-low-positive tumors was intermediate between that of the ER-positive and ER-negative groups. ER-low-positive/PR-positive tumors had a significantly worse prognosis than ER-positive tumors, and a trend toward favorable survival outcomes when compared to ER-negative tumors, although no significant difference was identified for the latter. In contrast, the ER-positive and ER-low-positive groups showed similar survival outcomes in the subset of tumors with a PR-negative status, both being significantly better than ER-negative tumors.

Conclusions: PR status as a surrogate marker of functional ER signaling provides critical information in this regard. These findings suggest that while ER-low-positive tumors are themselves heterogeneous, they often respond to endocrine treatment. Analysis of molecular signatures and standardization of therapeutic strategies are important to understand the biology of ER-low-positive tumors and to enable optimal treatment in the pursuit of individualized medicine.

Keywords: Breast cancer; Estrogen receptor; Estrogen receptor-low-positive; Progesterone receptor; Survival.

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