ArticleJournal of the National Cancer Institute2018
Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.
Article in Journal of the National Cancer Institute, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 85 citations in OpenAlex.
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- Long-term benefit from adjuvant tamoxifen therapy for ER+ HER2- breast cancer by PR positivity.International journal of cancer · 2026Trial
- Tamoxifen therapy benefit in luminal A and B breast cancer with 20-year follow-up.Journal of the National Cancer Institute · 2026Trial
- Progesterone receptor (PR) intra-tumor heterogeneity in premenopausal breast cancer: A secondary analysis of a randomized trial.International journal of cancer · 2026Trial
- Differential long-term tamoxifen therapy benefit by menopausal status in breast cancer patients: secondary analysis of a controlled randomized clinical trial.Journal of the National Cancer Institute · 2025Trial
- Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up.Acta oncologica (Stockholm, Sweden) · 2024Trial
- Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Trial
- 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
- Breast Cancer Liver Metastasis: Primary tumor predictors and histopathologic characteristics of metastatic lesions.Research square · 2026Article
- Spatial transcriptome revealed associated biomarkers for endocrine therapy response in HR-positive/HER2-negative early breast cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Expression of Estrogen Receptor Alpha and Ki-67 in Synchronous Canine Mammary Tumors.Journal of mammary gland biology and neoplasia · 2026Article
- Heterogeneity and immune microenvironment of early invasive estrogen receptor-positive breast cancer reveal an immune-rich subset.NPJ breast cancer · 2026Article
- Potential Targets and Biomarkers of Radionuclide Therapy in Breast Cancer.Cancer innovation · 2026Review
- Single amino-acid differences define H2B variants and modify chromatin accessibility to induce EMT in breast cancer.Oncogene · 2026Article
- Reproducibility of Ki67 Haralick entropy as a prognostic marker in estrogen receptor-positive HER2-negative breast cancer.American journal of clinical pathology · 2025Article
- An injury-associated lobular microniche is associated with the classical tumor cell phenotype in pancreatic cancer.Nature communications · 2025Article
- Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 9 institutions in 2 countries.
Funding
Abstract
Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.