ArticleJournal of the National Cancer Institute2024
Immune and gene-expression profiling in estrogen receptor low and negative early breast cancer.
Article in Journal of the National Cancer Institute, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between endocrine therapy and survival outcomes in estrogen receptor-low breast cancer: a systematic review and meta-analysis.The oncologist · 2026Pooled it
- PROMENADE: pembrolizumab for early ER-low/HER2-negative breast cancer, real-world French cohort.ESMO open · 2025Trial
- Endocrine Therapy Omission in Estrogen Receptor-Low (1-10%) Early Stage Breast Cancer: An Updated Analysis of the NCDB Database.Annals of surgical oncology · 2026Article
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Patient characteristics, treatment patterns, and survival across estrogen receptor expression subgroups in HER2-negative breast cancer: a population-based cohort study.The Lancet regional health. Europe · 2026Article
- Evolution of ER-cut-off definition in clinical trials for triple negative breast cancer: trends and patterns over 15 years.Breast (Edinburgh, Scotland) · 2026Review
- Risk stratification and relapse pattern in triple-negative breast cancer with pathological complete response after neoadjuvant treatment: the European GAMBIT real-world study.Nature communications · 2026Observational
- A Practical Immunohistochemistry-Based Model for Predicting Pathologic Complete Response in Estrogen Receptor-Strong Positive and HER2-Negative Breast Cancer.Journal of breast cancer · 2026Article
- Tailoring targeted therapies for younger women with ER-positive early-stage breast cancer.Nature reviews. Clinical oncology · 2026Review
- Germline BRCA1/2 Mutation Prevalence in Unselected ER-Low/HER2-Negative Breast Cancer.Annals of surgical oncology · 2026Article
- Estrogen Receptor-Low Positive (ER-Low) Breast Cancer: A Unique Clinical and Pathological Entity.Current oncology (Toronto, Ont.) · 2026Review
- Defining prognostic subgroups and treatment outcomes in estrogen receptor low-positive de novo metastatic breast cancer.Breast cancer research and treatment · 2026Observational
- Impact of estrogen receptor expression levels on chemo-responsiveness and prognosis of breast cancer patients treated with neoadjuvant chemotherapy.NPJ breast cancer · 2026Article
- Prognosis and endocrine therapy efficacy in early breast cancer with estrogen receptor low expression.Breast cancer research and treatment · 2026Article
- Adjuvant endocrine therapy in estrogen-low breast cancer in the era of CDKI: are we at another uncertain crossroads?Frontiers in oncology · 2026Review
- Reconsidering the definition of triple-negative breast cancer in the immune checkpoint inhibitor era: an optimal cut-off value for hormone receptor percentage of HER2-negative invasive breast cancer.British journal of cancer · 2026Review
- Distribution and molecular drivers of the 21-gene recurrence score in early breast cancer with low, intermediate, and high estrogen receptor expression.Frontiers in immunology · 2026Article
- DAXX and ATRX Expression in Canine Prostate and Bladder Cancer Identified by Immunohistochemistry-A Digital Quantitative Pilot Study.Veterinary sciences · 2025Article
- Prognosis and Biological Characteristics of ER-Low Metastatic Breast Cancer: Results from a Multicenter Cohort and the TONIC Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Molecular profiling of the Basal-like intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer.Genome medicine · 2025Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
backgroundThe cutoff of <1% positive cells to define estrogen receptor (ER) negativity by immunohistochemistry (IHC) in breast cancer (BC) is debated. We explored the tumor immune microenvironment and gene-expression profile of patients with early-stage HER2-negative ER-low (ER 1%-9%) BC, comparing them to ER-negative (ER <1%) and ER-intermediate (ER 10%-50%) tumors.
methodsAmong 921 patients with early-stage I-III, ER ≤50%, HER2-negative BCs, tumors were classified as ER-negative (n = 712), ER-low (n = 128), or ER-intermediate (n = 81). Tumor-infiltrating lymphocytes (TILs) were evaluated. CD8+, FOXP3+ cells, and PD-L1 status were assessed by IHC and quantified by digital pathology. We analyzed 776 BC-related genes in 116 samples. All tests were 2-sided at a <.05 significance level.
resultsER-low and ER-negative tumors exhibited similar median TILs, statistically significantly higher than ER-intermediate tumors. CD8/FOXP3 ratio and PD-L1 positivity rates were comparable between ER-low and ER-negative groups. These groups showed similar enrichment in basal-like intrinsic subtypes and comparable expression of immune-related genes. ER-low and ER-intermediate tumors showed significant transcriptomic differences. High TILs (≥30%) were associated with improved relapse-free survival (RFS) in ER-low (5-year RFS 78.6% vs 66.2%, log-rank P = .033, hazard ratio [HR] 0.37 [95% CI = 0.15 to 0.96]) and ER-negative patients (5-year RFS 85.2% vs 69.8%, log-rank P < .001, HR 0.41 [95% CI = 0.27 to 0.60]).
conclusionsER-low and ER-negative tumors are similar biological and molecular entities, supporting their comparable clinical outcomes and treatment responses, including to immunotherapy. Our findings contribute to the growing evidence calling for a reevaluation of ER-positive BC classification and management, aligning ER-low and ER-negative tumors more closely.
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