ArticleJCO precision oncology2022
APOBEC Mutational Signatures in Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers Are Associated With Poor Outcomes on CDK4/6 Inhibitors and Endocrine Therapy.
Article in JCO precision oncology, 2022. 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 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- Genomic Predictive Biomarkers in Breast Cancer: TheInternational journal of molecular sciences · 2025Review
- Tumor mutational burden status and clinical characteristics of invasive lobular carcinoma of the breast.Breast cancer (Tokyo, Japan) · 2025Article
- Molecular Basis of Breast Tumor Heterogeneity.Advances in experimental medicine and biology · 2025Review
- APOBEC in breast cancer: a dual player in tumor evolution and therapeutic response.Frontiers in molecular biosciences · 2025Review
- Review
- Targeting APOBECs in cancer: It's about timing.Cancer cell · 2024Article
- Emerging systemic therapy options beyond CDK4/6 inhibitors for hormone receptor-positive HER2-negative advanced breast cancer.NPJ breast cancer · 2023Review
- Tumor Mutational Burden in Breast Cancer: Current Evidence, Challenges, and Opportunities.Cancers · 2023Review
- Aberrant APOBEC3B Expression in Breast Cancer Is Linked to Proliferation and Cell Cycle Phase.Cells · 2023Article
- APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential.Journal of hematology & oncology · 2023Review
- Involvement of APOBEC3A/B Deletion in Mouse Mammary Tumor Virus (MMTV)-like Positive Human Breast Cancer.Diagnostics (Basel, Switzerland) · 2023Article
Corrections and comments
- Erratum issuedErratum.2022
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAPOBEC mutagenesis underlies somatic evolution and accounts for tumor heterogeneity in several cancers, including breast cancer (BC). In this study, we evaluated the characteristics of a real-world cohort for time-to-treatment discontinuation (TTD) and overall survival on CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) and immune checkpoint inhibitors.
methodsComprehensive genomic profiling results from 29,833 BC samples were analyzed for tumor mutational burden and APOBEC signatures. For clinical outcomes, a deidentified nationwide (United States-based) BC Clinico-Genomic Database (CGDB) was evaluated with log-rank and Cox models. Patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) BC who received first-line ET and CDK4/6i were included. Eligible patients from Mayo Clinic and Duke University were HR+ HER2- BC with sequencing data between September 2013 and July 2020.
resultsOf 29,833 samples sequenced, 7.9% were APOBEC+ with a high rate in invasive lobular carcinoma (16.7%) and in metastatic tumors (9.7%) relative to locally biopsied BC (4.3%;
conclusionAPOBEC+ HR+ HER2- patients had shorter TTD on first-line ET plus CDK4/6i relative to APOBEC- patients. Further research is needed to optimize the treatment of APOBEC+ HR+ HER2- BC and to investigate the efficacy of immunotherapeutic strategies in this population.
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