ArticleBreast cancer research and treatment2020
Actionable co-alterations in breast tumors with pathogenic mutations in the homologous recombination DNA damage repair pathway.
Article in Breast cancer research and treatment, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Characterization of the HER2 status in BRCA-mutated breast cancer: a single institutional series and systematic review with pooled analysis.ESMO open · 2022Pooled it
- Genetic Alterations, Therapy Response, and Survival Among Patients With Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.JAMA network open · 2025Trial
- Article
- Molecular Basis of Breast Tumor Heterogeneity.Advances in experimental medicine and biology · 2025Review
- Distribution of PD-L1, TROP2 and HER2- "lowness" in early triple-negative breast cancer: an opportunity for treatment de-escalation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- A novel targeted NGS panel identifies numerous homologous recombination deficiency (HRD)-associated gene mutations in addition to known BRCA mutations.Diagnostic pathology · 2024Article
- Mechanism of PARP inhibitor resistance and potential overcoming strategies.Genes & diseases · 2024Review
- A BRCA2 germline mutation and high expression of immune checkpoints in a TNBC patient.Cell death discovery · 2023Article
- A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer.JCO precision oncology · 2023Article
- Next-Generation Sequencing and Triple-Negative Breast Cancer: Insights and Applications.International journal of molecular sciences · 2023Review
- Comparison of the mutational profiles of neuroendocrine breast tumours, invasive ductal carcinomas and pancreatic neuroendocrine carcinomas.Oncogenesis · 2022Article
- The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy.Journal of experimental & clinical cancer research : CR · 2022Review
- Multi-Gene Testing Overview with a Clinical Perspective in Metastatic Triple-Negative Breast Cancer.International journal of molecular sciences · 2021Review
- Practical considerations for optimising homologous recombination repair mutation testing in patients with metastatic prostate cancer.The journal of pathology. Clinical research · 2021Review
- Checkpoint inhibitor therapy for metastatic triple-negative breast cancer.Cancer metastasis reviews · 2021Review
- Mismatch repair-deficient hormone receptor-positive breast cancers: Biology and pathological characterization.Cancer cell international · 2021Review
- A comprehensive analysis of somatic alterations in Chinese ovarian cancer patients.Scientific reports · 2021Article
- Mutational spectrum and precision oncology for biliary tract carcinoma.Theranostics · 2021Article
- Decoding Cancer Variants of Unknown Significance for Helicase-Nuclease-RPA Complexes Orchestrating DNA Repair During Transcription and Replication.Frontiers in molecular biosciences · 2021Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeHomologous recombination (HR)-deficient breast tumors may have genomic alterations that predict response to treatment with PARP inhibitors and other targeted therapies.
methodsComprehensive molecular profiles of 4647 breast tumors performed at Caris Life Sciences using 592-gene NGS were reviewed to identify somatic pathogenic mutations in HR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, KMT2D, MRE11, NBN, PALB2, RAD50/51/51B, and WRN, as well as 41 markers that may be associated with treatment response to targeted anticancer therapies.
results17.9% of breast tumors had HR mutations (HR-MT, 831/4647) [ER/PR+ , HER2- 18.3%, n = 2183; TNBC 18.2%, n = 1568; ER/PR+ , HER2+ 15.6%, n = 237; ER/PR-, HER2+ 12.9%, n = 217; unknown n = 442]. Mean TMB was higher for HR-MT tumors across subtypes (9.2 mut/Mb vs 7.6 h-wild type (HR-WT), p ≤ 0.0001) and independent of microsatellite status. MSI-H/dMMR was more frequent among HR-MT tumors (2.1% HR-MT vs 0.2% HR-WT, p ≤ 0.0001), as was tumor PD-L1 overexpression (13.2% HR-MT vs 11.0% HR-WT, p = 0.08). Additional co-alterations were similar between HR-MT and HR-WT, with the exception of PIK3CA (30.3% HR-WT vs 26.4% HR-MT, p = 0.024) and AKT1 (3.7% HR-WT vs 2.1% HR-MT, p = 0.021). AR overexpression and PIK3CA mutations were more common among ER/PR+ tumors. ERBB2 mutations were seen in both HER2+ and HER2- tumors.
conclusionsHR-MT was common across breast cancer subtypes and co-occurred more frequently with markers of response to immunotherapy (MSI-H/dMMR, TMB) compared to HR-WT tumors. Mutations were identified in both HR-MT and HR-WT tumors that suggest other targets for treatment. Clinical trials combining HRD-targeted agents and immunotherapy are underway and could be enriched through comprehensive molecular profiling.
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