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Review
. 2022 Nov 24:13:1015388.
doi: 10.3389/fendo.2022.1015388. eCollection 2022.

Clinical implication of low estrogen receptor (ER-low) expression in breast cancer

Tomás Reinert  1   2 , Fanny Cascelli  3 , Cristiano Augusto Andrade de Resende  4 , Aline Coelho Gonçalves  5 , Vania Sanchez Prette Godo  3 , Carlos Henrique Barrios  1   2
Affiliations
Review

Clinical implication of low estrogen receptor (ER-low) expression in breast cancer

Tomás Reinert et al. Front Endocrinol (Lausanne). .

Abstract

Breast cancer is a heterogeneous disease, and the estrogen receptor (ER) remains the most important biomarker in breast oncology. Most guidelines set a positive expression threshold of 1% staining in immunohistochemistry (IHC) to define ER positivity. However, different expression levels may be associated with diverse degrees of sensitivity to endocrine therapy as ER expression may impact breast cancer molecular biology as a continuous variable. ER-lo tumors, defined as those with 1-10% ER expression, represent a relatively small subgroup of breast cancer patients, with an estimated prevalence of 2-7%. These tumors are similar to ERneg disease in their molecular landscape, clinicopathological characteristics, prognosis, and response to therapy. Nevertheless, a proportion may retain some degree of ER signaling dependency, and the possibility of responding to some degree to endocrine therapy cannot be completely ruled out. This review article discusses the most important considerations regarding the definition of ER positivity, pathology assessment, prognosis, and therapeutic implication of ERlo breast cancer from the medical oncology perspective.

Keywords: ER low positive; ESR1; breast cancer; endocrine therapy; estrogen receptor.

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Conflict of interest statement

The authors declare the following potential conflicts of interest, although none are directly related to the writing and publication of the present manuscript. TR- Research funding: AstraZeneca, Libbs Speaker honoraria: AstraZeneca, Pfizer, Novartis, MSD, Daichi-Sankyo, Libbs, Lily Advisory board: AstraZeneca, Daichii-Sankyo, Novartis, MSD. CR- Speaker honoraria: AstraZeneca, BMS, Daiichi-Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, United Medical Advisory board: BMS, Roche. AG- Speaker honoraria: Roche, Novartis, Eisai, Eli-Lilly, Pfizer; Daichii Sankyo, Astrazeneca Advisory board: Roche, Eli-Lilly, United Medical, Pfizer. CB- Stock and Other Ownership Interests: Biomarker, MedSIR, Tummi Speaker Honoraria: Novartis, Roche/Genentech, Pfizer, GlaxoSmithKline, Sanofi, Boehringer Ingelheim, Eisai Consulting or Advisory Role: Boehringer Ingelheim, Roche/Genentech, Novartis, GlaxoSmithKline, Eisai, Pfizer, AstraZeneca, Libbs, MSD Oncology, United Medical Research Funding: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Roche/Genentech, Lilly, Sanofi, Taiho Pharmaceutical, Mylan, Merrimack, Merck, AbbVie, Astellas Pharma, Biomarin, Bristol-Myers Squibb, Daiichi Sankyo, Abraxis BioScience, AB Science, Asana Biosciences, Medivation, Exelixis, ImClone Systems, LEO Pharma, Millennium, Janssen, Atlantis Clinica, INC Research, Halozyme, Covance, Celgene, inVentiv HealthT Travel, Accommodations, Expenses: Roche/Genentech, Novartis, Pfizer, BMS Brazil, AstraZeneca, MSD Oncology. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Reprinted with permission from Fusco N et al., 2021 (16). Schematic representation of the standard operating procedures for an appropriate low ER status assessment. After the bioptic or surgical excision, the sample should be transferred to the pathology lab using a temperature-controlled system. Of note, the cold ischemia time should not exceed 1 hour. The preservation of the sample for transport can be either under vacuum or in 4% neutral buffered formalin. The time before sampling should range from 6 to 72 hours. After tissue processing, the pathologist should select the most representative sample and be subjected to immunohistochemistry for analysis, which can rely on validated digital pathology tools. The biomarker report in case of low ER positivity requires information on the percentage of positive neoplastic cells, staining intensity, and status of the internal controls. According to the ASCO/CAP guidelines, a note should be added for all ERlo tumors. ER, estrogen receptor; NBF, neutral buffered formalin; FFPE, formalin-fixed paraffin-embedded; ASCO, American Society of Clinical Oncology; CAP, College of American Pathologists.
See this image and copyright information in PMC

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