ArticlePLoS genetics2023
ESR1 gene amplification and MAP3K mutations are selected during adjuvant endocrine therapies in relapsing Hormone Receptor-positive, HER2-negative breast cancer (HR+ HER2- BC).
Article in PLoS genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- A predictive endocrine resistance index accurately stratifies luminal breast cancer treatment responders and nonresponders.The Journal of clinical investigation · 2025Trial
- Identification of actionable targets using DEPArray-based sorting of pure carcinoma and stromal populations from formalin-fixed paraffin-embedded tissues followed by shallow whole-genome sequencing.The Journal of pathology · 2026Article
- Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer.Molecular biomedicine · 2025Review
- Article
- Long-term Multimodal Recording Reveals Epigenetic Adaptation Routes in Dormant Breast Cancer Cells.Cancer discovery · 2024Article
- Prognostic impact of tumor-associated neutrophils in breast cancer.International journal of clinical and experimental pathology · 2024Article
- Revisiting Estrogen for the Treatment of Endocrine-Resistant Breast Cancer: Novel Therapeutic Approaches.Cancers · 2023Review
- High expression of the RET receptor tyrosine kinase and its ligand GDNF identifies a high-risk subset of estrogen receptor positive breast cancer.Breast cancer research and treatment · 2023Article
- Tamoxifen Response at Single Cell Resolution in Estrogen Receptor-Positive Primary Human Breast Tumors.bioRxiv : the preprint server for biology · 2023Article
- St. Gallen/Vienna 2023: Optimization of Treatment for Patients with Primary Breast Cancer - A Brief Summary of the Consensus Discussion.Breast care (Basel, Switzerland) · 2023Review
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Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundPrevious studies have provided a comprehensive picture of genomic alterations in primary and metastatic Hormone Receptor (HR)-positive, Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer (HR+ HER2- BC). However, the evolution of the genomic landscape of HR+ HER2- BC during adjuvant endocrine therapies (ETs) remains poorly investigated. METHODS AND
findingsWe performed a genomic characterization of surgically resected HR+ HER2- BC patients relapsing during or at the completion of adjuvant ET. Using a customized panel, we comprehensively evaluated gene mutations and copy number variation (CNV) in paired primary and metastatic specimens. After retrieval and quality/quantity check of tumor specimens from an original cohort of 204 cases, 74 matched tumor samples were successfully evaluated for DNA mutations and CNV analysis. Along with previously reported genomic alterations, including PIK3CA, TP53, CDH1, GATA3 and ESR1 mutations/deletions, we found that ESR1 gene amplification (confirmed by FISH) and MAP3K mutations were enriched in metastatic lesions as compared to matched primary tumors. These alterations were exclusively found in patients treated with adjuvant aromatase inhibitors or LHRH analogs plus tamoxifen, but not in patients treated with tamoxifen alone. Patients with tumors bearing MAP3K mutations in metastatic lesions had significantly worse distant relapse-free survival (hazard ratio [HR] 3.4, 95% CI 1.52-7.70, p value 0.003) and worse overall survival (HR 5.2, 95% CI 2.10-12.8, p-value < 0.001) independently of other clinically relevant patient- and tumor-related variables.
conclusionsESR1 amplification and activating MAP3K mutations are potential drivers of acquired resistance to adjuvant ETs employing estrogen deprivation in HR+ HER2- BC. MAP3K mutations are associated with worse prognosis in patients with metastatic disease.
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