ArticleMolecular oncology2018
Intratumor heterogeneity defines treatment-resistant HER2+ breast tumors.
Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed.
- Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma.Cancer medicine · 2023Trial
- Impact of HER2 Heterogeneity on Treatment Response of Early-Stage HER2-Positive Breast Cancer: Phase II Neoadjuvant Clinical Trial of T-DM1 Combined with Pertuzumab.Cancer discovery · 2021Trial
- Proteomic profiling of CD133 + and CD326 + (EpCAM) subpopulations in A549 cells: insights into pluripotency and tumor heterogeneity.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- HER2 Heterogeneous Breast Cancer Models Reveal Novel Therapeutic Targets and Subclonal Dynamics during Evolution to Resistance to HER2-Targeted Therapies.Cancer discovery · 2026Article
- Review
- Hierarchical Tissue-Specific Modeling of Pathology Images Predicts Response in HER2+ Breast Cancer.Cyborg and bionic systems (Washington, D.C.) · 2026Article
- Whole-genome landscapes of 1,364 breast cancers.Nature · 2026Article
- HER2 Heterogeneity in Breast Cancer: Biological Basis, Clinical Implications, and Therapeutic Strategies.Breast cancer (Dove Medical Press) · 2026Review
- Review
- Advancements in antibody-drug conjugates as cancer therapeutics.Journal of the National Cancer Center · 2025Review
- Response to anti-HER2 neoadjuvant chemotherapy in HER2-positive invasive breast cancers with different HER2 FISH patterns.Journal of clinical pathology · 2025Article
- HER2-Driven Breast Cancer: Role of the Chaperonin HSP90 in Modulating Response to Trastuzumab-Based Therapeutic Combinations.International journal of molecular sciences · 2025Article
- Quantitative [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Clonal dispersal is associated with tumor heterogeneity and poor prognosis in colorectal cancer.iScience · 2025Article
- Cancer immune evasion, immunoediting and intratumour heterogeneity.Nature reviews. Immunology · 2025Review
- Origins and impact of extrachromosomal DNA.Nature · 2024Article
- A glimpse into the future: Integrating artificial intelligence for precision HER2-positive breast cancer management.iMetaOmics · 2024Review
- Navigating HER2-Low Testing in Invasive Breast Cancer: Update Recommendations for Pathologists.Journal of personalized medicine · 2024Review
- Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives.Nature reviews. Clinical oncology · 2024Review
- An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer.Scientific reports · 2024Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
Targeted therapy for patients with HER2-positive (HER2+) breast cancer has improved overall survival, but many patients still suffer relapse and death from the disease. Intratumor heterogeneity of both estrogen receptor (ER) and HER2 expression has been proposed to play a key role in treatment failure, but little work has been done to comprehensively study this heterogeneity at the single-cell level. In this study, we explored the clinical impact of intratumor heterogeneity of ER protein expression, HER2 protein expression, and HER2 gene copy number alterations. Using combined immunofluorescence and in situ hybridization on tissue sections followed by a validated computational approach, we analyzed more than 13 000 single tumor cells across 37 HER2+ breast tumors. The samples were taken both before and after neoadjuvant chemotherapy plus HER2-targeted treatment, enabling us to study tumor evolution as well. We found that intratumor heterogeneity for HER2 copy number varied substantially between patient samples. Highly heterogeneous tumors were associated with significantly shorter disease-free survival and fewer long-term survivors. Patients for which HER2 characteristics did not change during treatment had a significantly worse outcome. This work shows the impact of intratumor heterogeneity in molecular diagnostics for treatment selection in HER2+ breast cancer patients and the power of computational scoring methods to evaluate in situ molecular markers in tissue biopsies.
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