ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Global Transcriptional Complexity of Estrogen Receptor-Low Positive Breast Cancers in the Prospective Swedish Population-Based SCAN-B Cohort.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 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
- 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
- Real-world outcomes of datopotamab deruxtecan after trastuzumab deruxtecan in hormone receptor-positive, HER2-negative metastatic breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- 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
- Molecular profiling of the Basal-like intrinsic molecular subtype in primary ER-positive HER2-negative breast cancer.Genome medicine · 2025Article
- Predicting neoadjuvant chemotherapy treatment response in hormone- receptor-positive/HER2-negative breast cancer - results from the Swedish SCAN-B population-based cohort.Acta oncologica (Stockholm, Sweden) · 2025Article
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7 authors.
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Abstract
purposeThere is uncertainty whether estrogen receptor (ER)-low tumors with 1% to 10% IHC staining of nuclei represent a distinct molecular biological entity of breast cancer, posing significant challenges for their clinical management and the development of novel therapies. We aimed to elucidate ER-low tumor biology. EXPERIMENTAL
designWe analyzed primary breast tumors included in the Swedish population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) cohort, 2% (n = 174) of which were classified as ER-low. Transcriptional patterns, tumor inflammatory infiltration, and prognosis were compared between ER-low versus ER-negative (ER-neg; 0%) and ER-positive (ER-pos; >10%) tumors.
resultsThe transcriptomes of ER-low and ER-neg tumors remarkably overlapped, displaying predominantly nonluminal PAM50 subtypes and downregulated ER signaling. All triple-negative breast cancer (TNBC) molecular subtypes were represented within ER-low/HER2-negative breast cancer. Unsupervised clustering algorithms failed to segregate ER-low/HER2-negative from TNBC tumors, and only two genes showed significant differential expression above a 1.5-fold difference between the groups. However, borderline ER-low tumors (with exactly 10% ER) were mostly assigned labels associated with luminal disease biology, suggesting possible endocrine responsiveness. Lymphocyte infiltration was comparable between ER-low and ER-neg but was significantly higher relative to ER-pos tumors. Within ER-low/HER2-negative disease, hormone receptor positivity and low/intermediate PAM50 risk of recurrence score inferred from RNA sequencing data and lymphocyte fraction ≥30% were respectively associated with a better prognosis.
conclusionsER-low/HER2-negative is not a distinct breast cancer molecular biological entity but an integral part of TNBC, deserving similar treatments. Nonetheless, a few borderline cases with moderately active ER signaling can potentially respond to endocrine therapies. Hormone receptor-related signatures and tumor-infiltrating lymphocytes may stratify ER-low/HER2-negative tumors according to the risk of recurrence. The true benefit of endocrine therapies in ER-low breast cancer requires prospective investigation.
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