ArticleBreast cancer research and treatment2018
Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival.
Article in Breast cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
7 citing papers in PubMed, 12 citations in OpenAlex.
- The effect of the number of negative lymph nodes removed during surgery on the survival and recurrence rates of patients with breast cancer after surgery.BMC surgery · 2026Article
- Mixed Molecular Subtypes Coexist in Estrogen Receptor Heterogeneous Primary Breast Cancers.JCO precision oncology · 2025Article
- Review
- Tumor Heterogeneity of Breast Cancer Assessed with Computed Tomography Texture Analysis: Association with Disease-Free Survival and Clinicopathological Prognostic Factor.Diagnostics (Basel, Switzerland) · 2023Article
- Tumor heterogeneity and the dilemma of antioxidant therapies in cancer.Annals of translational medicine · 2022Article
- Beyond Genetics: Metastasis as an Adaptive Response in Breast Cancer.International journal of molecular sciences · 2022Review
- Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments.Medical sciences (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe purpose of the study was to define quantitative measures of intra-tumor heterogeneity in breast cancer based on histopathology data gathered from multiple samples on individual patients and determine their association with distant recurrence-free survival (DRFS).
methodsWe collected data from 971 invasive breast cancers, from 1st January 2000 to 23rd March 2014, that underwent repeat tumor sampling at our institution. We defined and calculated 31 measures of intra-tumor heterogeneity including ER, PR, and HER2 immunohistochemistry (IHC), proliferation, EGFR IHC, grade, and histology. For each heterogeneity measure, Cox proportional hazards models were used to determine whether patients with heterogeneous disease had different distant recurrence-free survival (DRFS) than those with homogeneous disease.
resultsThe presence of heterogeneity in ER percentage staining was prognostic of reduced DRFS with a hazard ratio of 4.26 (95% CI 2.22-8.18, p < 0.00002). It remained significant after controlling for the ER status itself (p < 0.00062) and for patients that had chemotherapy (p < 0.00032). Most of the heterogeneity measures did not show any association with DRFS despite the considerable sample size.
conclusionsIntra-tumor heterogeneity of ER receptor status may be a predictor of patient DRFS. Histopathologic data from multiple tissue samples may offer a view of tumor heterogeneity and assess recurrence risk.
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