Academic Journal
The impact of intratumor heterogeneity on outcome and resistance to therapy in primary breast cancer: a systematic review.
| Τίτλος: | The impact of intratumor heterogeneity on outcome and resistance to therapy in primary breast cancer: a systematic review. |
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| Συγγραφείς: | Dianati A; Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands. aria.dianati@maastrichtuniversity.nl.; Department of Epidemiology, NUTRIM School of Nutrition and Translational Research in Metabolism, , Maastricht University, Maastricht, The Netherlands. aria.dianati@maastrichtuniversity.nl., Dekker A; Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands., Wesselius A; Department of Epidemiology, NUTRIM School of Nutrition and Translational Research in Metabolism, , Maastricht University, Maastricht, The Netherlands., Wee L; Department of Radiation Oncology (Maastro), GROW Research Institute for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, The Netherlands. |
| Πηγή: | Medical oncology (Northwood, London, England) [Med Oncol] 2026 Oct 03; Vol. 43 (11). Date of Electronic Publication: 2026 Oct 03. |
| Τύπος έκδοσης: | Journal Article; Systematic Review |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Springer Country of Publication: United States NLM ID: 9435512 Publication Model: Electronic Cited Medium: Internet ISSN: 1559-131X (Electronic) Linking ISSN: 13570560 NLM ISO Abbreviation: Med Oncol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2011- : New York : Springer Original Publication: Northwood, Middlesex, England : Science and Technology Letters, c1994- |
| Ιατρικοί όροι (MeSH): | Breast Neoplasms*/pathology , Breast Neoplasms*/drug therapy , Breast Neoplasms*/genetics , Drug Resistance, Neoplasm*/genetics , Genetic Heterogeneity*, Humans ; Female ; Radiomics |
| Περίληψη: | Intratumor heterogeneity (ITH), the coexistence of diverse subclones within a single tumor, may pose a major challenge to effective chemotherapy in breast cancer. This cellular diversity contributes to treatment failure, residual disease, and early relapse by enabling tumor adaptation and therapeutic resistance. Although increasingly recognized as a critical feature of breast cancer biology, it remains under-investigated and has not yet been integrated into routine clinical care. This review synthesizes current evidence on the role of ITH in chemotherapy resistance in primary breast cancer. Following PRISMA guidelines, we searched MEDLINE via PubMed, Web of Science, and Scopus through June 2026. Twelve studies met the inclusion criteria. Data were extracted on tumor subtypes, study design, ITH assessment modality (genomic, transcriptomic, radiomic, or immunologic), sampling method, treatment type, and outcomes. Among the 12 included studies, covering triple-negative, HER2-positive, and mixed breast cancer cohorts, high or increasing ITH, assessed using molecular or imaging-based methods, was associated with reduced sensitivity to chemotherapy. Proposed mechanisms underlying resistance included clonal selection, transcriptional plasticity, immune exclusion, and phenotypic drift. Radiomic and MRI-derived features may provide additional predictive value beyond molecular classifiers, and integrated radiomic-genomic models outperformed either modality alone in identifying patients with poor treatment response. In conclusion, current evidence suggests that ITH may be associated with chemotherapy resistance in primary breast cancer through several biological mechanisms. Integrating radiomic and imaging-based assessments with molecular profiling has the potential to improve the prediction of treatment response and facilitate monitoring of changes in tumor heterogeneity during therapy, although further prospective validation is needed before routine clinical implementation.Protocol Registration Number at PROSPERO: CRD42024533885. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. |
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| Contributed Indexing: | Keywords: Breast cancer; Chemotherapy; ITH; Treatment resistance |
| Entry Date(s): | Date Created: 20261003 Date Completed: 20261003 Latest Revision: 20261009 |
| Update Code: | 20261009 |
| PubMed Central ID: | PMC13634018 |
| DOI: | 10.1007/s12032-026-03426-z |
| PMID: | 42828601 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1559-131X |
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| DOI: | 10.1007/s12032-026-03426-z |