Trial reportBreast cancer research : BCR2012
Low expression levels of ATM may substitute for CHEK2 /TP53 mutations predicting resistance towards anthracycline and mitomycin chemotherapy in breast cancer.
Trial report in Breast cancer research : BCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Tanshinone IIA is synergistic with the PARP inhibitor olaparib in inducing BRCAs-proficient and -deficient triple-negative breast cancer cell apoptosis.Medical oncology (Northwood, London, England) · 2025Article
- Moderate-Low Risk Breast Cancer Gene Expression in a Romanian Population.International journal of molecular sciences · 2025Article
- Breast cancer genomic analyses reveal genes, mutations, and signaling networks.Functional & integrative genomics · 2024Article
- p53 Dysregulation in Breast Cancer: Insights on Mutations in theInternational journal of molecular sciences · 2023Article
- A gene signature driven by abnormally methylated DEGs was developed for TP53 wild-type ovarian cancer samples by integrative omics analysis of DNA methylation and gene expression data.Annals of translational medicine · 2023Article
- Clonal evolution in primary breast cancers under sequential epirubicin and docetaxel monotherapy.Genome medicine · 2022Article
- Functions of Breast Cancer Predisposition Genes: Implications for Clinical Management.International journal of molecular sciences · 2022Review
- Article
- Co-Expression and Combined Prognostic Value of CSPG4 and PDL1 inFrontiers in oncology · 2022Article
- Influence ofCancers · 2021Article
- Genomic alteration profiles of lung cancer and their relationship to clinical features and prognosis value using individualized genetic testing.Journal of thoracic disease · 2021Article
- Review
- Prevalence of Recurrent Mutations Predisposing to Breast Cancer in Early-Onset Breast Cancer Patients from Poland.Cancers · 2020Article
- CHEK2 Mutation in Patient with Multiple Endocrine Glands Tumors. Case Report.International journal of environmental research and public health · 2020Article
- The novel microRNAs hsa-miR-nov7 and hsa-miR-nov3 are over-expressed in locally advanced breast cancer.PloS one · 2020Article
- Comparison of Patient Susceptibility Genes Across Breast Cancer: Implications for Prognosis and Therapeutic Outcomes.Pharmacogenomics and personalized medicine · 2020Review
- Expression Signatures of Cisplatin- and Trametinib-Treated Early-Stage Medaka Melanomas.G3 (Bethesda, Md.) · 2019Article
- Recent advances of therapeutic targets based on the molecular signature in breast cancer: genetic mutations and implications for current treatment paradigms.Journal of hematology & oncology · 2019Review
- Molecular features unique to glioblastoma radiation resistant residual cells may affect patient outcome - a short report.Cellular oncology (Dordrecht, Netherlands) · 2019Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATM's potential role in resistance to chemotherapy.
methodsWe sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status.
resultsWhile ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% percentiles) or mutations inactivating TP53 or CHEK2 robustly predicted anthracycline resistance (P-values varying between 0.001 and 0.027 depending on the percentile used to define "low" ATM levels). These results were confirmed in an independent cohort of 109 patients treated with epirubicin monotherapy. In contrast, ATM-levels were not suppressed in resistant tumors harboring TP53 or CHEK2 mutations (P > 0.5).
conclusionsOur data indicate loss of function of the ATM-Chk2-p53 cascade to be strongly associated with resistance to anthracycline/mitomycin-containing chemotherapy in breast cancer.
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