ArticleNature communications2019
Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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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
37 citing papers in PubMed, 60 citations in OpenAlex.
- HER2 status change in residual breast carcinoma after neoadjuvant HER2-targeted therapy in patients with HER2-positive breast cancer.Breast cancer research and treatment · 2026Article
- Spatial habitat radiomics predicts tertiary lymphoid structure status and identifies an IDO1Journal for immunotherapy of cancer · 2026Article
- Genome-level selection in tumors as a universal marker of resistance to therapy.Nature communications · 2025Article
- HER2-Driven Breast Cancer: Role of the Chaperonin HSP90 in Modulating Response to Trastuzumab-Based Therapeutic Combinations.International journal of molecular sciences · 2025Article
- Minimal residue disease detection in early-stage breast cancer: a review.Molecular biology reports · 2025Review
- Quantitative systems pharmacology modeling of tumor heterogeneity in response to BH3-mimetics using virtual tumors calibrated with cell viability assays.CPT: pharmacometrics & systems pharmacology · 2024Article
- Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives.Nature reviews. Clinical oncology · 2024Review
- Modeling the Effect of Spatial Structure on Solid Tumor Evolution and Circulating Tumor DNA Composition.Cancers · 2024Article
- Modeling the effect of spatial structure on solid tumor evolution and ctDNA composition.bioRxiv : the preprint server for biology · 2023Article
- Clinical-genomic determinants of immune checkpoint blockade response in head and neck squamous cell carcinoma.The Journal of clinical investigation · 2023Article
- Treatment of evolving cancers will require dynamic decision support.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Review
- Review
- Radiomic tumor phenotypes augment molecular profiling in predicting recurrence free survival after breast neoadjuvant chemotherapy.Communications medicine · 2023Article
- Unlocking the Resistance to Anti-HER2 Treatments in Breast Cancer: The Issue of HER2 Spatial Distribution.Cancers · 2023Review
- Temporal and spatial topography of cell proliferation in cancer.Nature cell biology · 2022Article
- Sensei: how many samples to tell a change in cell type abundance?BMC bioinformatics · 2022Article
- Liquid Biopsy and Tissue Biopsy Comparison with Digital PCR and IHC/FISH for HER2 Amplification Detection in Breast Cancer Patients.Journal of Cancer · 2022Article
- Heterogeneity of Circulating Tumor Cell-Associated Genomic Gains in Breast Cancer and Its Association with the Host Immune Response.Cancer research · 2021Article
- Tumors Are Evolutionary Island-Like Ecosystems.Genome biology and evolution · 2021Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
Genomic changes observed across treatment may result from either clonal evolution or geographically disparate sampling of heterogeneous tumors. Here we use computational modeling based on analysis of fifteen primary breast tumors and find that apparent clonal change between two tumor samples can frequently be explained by pre-treatment heterogeneity, such that at least two regions are necessary to detect treatment-induced clonal shifts. To assess for clonal replacement, we devise a summary statistic based on whole-exome sequencing of a pre-treatment biopsy and multi-region sampling of the post-treatment surgical specimen and apply this measure to five breast tumors treated with neoadjuvant HER2-targeted therapy. Two tumors underwent clonal replacement with treatment, and mathematical modeling indicates these two tumors had resistant subclones prior to treatment and rates of resistance-related genomic changes that were substantially larger than previous estimates. Our results provide a needed framework to incorporate primary tumor heterogeneity in investigating the evolution of resistance.
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Registered trials
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.