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    BIOMARKER:

    HRD + BRCA1 mutation

    i
    Other names: BRCA1, BRCC1, PPP1R53, RNF53, Breast cancer 1, early onset, HRD, Homologous Recombination Deficiency
    Entrez ID:
    672
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    12ms
    An evaluation of talazoparib plus enzalutamide for the treatment of metastatic castration-resistant prostate cancer. (PubMed, Expert Rev Anticancer Ther)
    Genomic markers for homologous recombination deficiency (HRD) are other potential drivers of response to PARPi/ARPI combination. Further investigation is needed to refine treatment strategies, including targeting non-HRR mutations, and to expand the role of this combination therapy in earlier stages of prostate cancer.
    Review • Journal • BRCA Biomarker • PARP Biomarker • Metastases
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
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    Talzenna (talazoparib) • Xtandi (enzalutamide)
    12ms
    Niraparib in Tumors Metastatic to the CNS (clinicaltrials.gov)
    P2, N=20, Recruiting, Massachusetts General Hospital | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BAP1 (BRCA1 Associated Protein 1) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • XRCC2 (X-Ray Repair Cross Complementing 2) • RAD54B (RAD54 Homolog B) • XRCC3 (X-Ray Repair Cross Complementing 3)
    |
    BRCA1 mutation • HRD • ATM mutation • PALB2 mutation • BAP1 mutation • BRIP1 mutation • HRD + BRCA1 mutation • RAD51C mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • MRE11A mutation • RAD54L mutation • NBN mutation • HRD signature
    |
    Zejula (niraparib)
    12ms
    Can Morphology and Immune Infiltration Predict the Homologous Recombination Deficiency Status in Newly Diagnosed High-Grade Serous Ovarian Carcinoma? (PubMed, Arch Pathol Lab Med)
    The combination of these 3 criteria showed high specificity (0.99; 95% CI, 0.97-0.99) but low sensitivity (0.07; 95% CI, 0.04-0.10). The morphology of HGSOC correlates with HRD status and BRCA status but cannot substitute for molecular analysis in daily practice.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
    |
    Myriad myChoice® CDx Plus
    1year
    BRCA loss of function including BRCA1 DNA-methylation, but not BRCA-unrelated homologous recombination deficiency, is associated with platinum hypersensitivity in high-grade ovarian cancer. (PubMed, Clin Epigenetics)
    In HGOC BRCA mutational status together with BRCA1-methylation exhibit the best predictive power for favorable clinical outcome and thus high sensitivity to platinum-based therapy, whereas BRCA-unrelated HRD positivity was not associated with improved platinum sensitivity.
    Journal • BRCA Biomarker • PARP Biomarker • Epigenetic controller
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    BRCA1 mutation • HRD • BRCA wild-type • HRD + BRCA1 mutation • BRCA mutation • BRCA1 expression
    1year
    Poly (ADP-Ribose) Polymerase Inhibitor Olaparib-Resistant BRCA1-Mutant Ovarian Cancer Cells Demonstrate Differential Sensitivity to PARP Inhibitor Rechallenge. (PubMed, Cells)
    UWB-OlaJR exhibits varying sensitivity to PARPis, showing cross-resistance to veliparib and talazoparib, and sensitivity with increased cytotoxicity to niraparib and rucaparib. Moreover, S1 nuclease fiber assay shows that niraparib and rucaparib induce greater DNA single-strand gaps than other PARPis, leading to increased DNA damage and cell death. Our study provides novel insights into differential PARPi sensitivity in olaparib-resistant BRCA-mutant OvCa, which requires further investigation of inter-agent differences in large prospective studies.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • Zejula (niraparib) • Rubraca (rucaparib) • veliparib (ABT-888)
    1year
    Olaparib monotherapy in advanced triple-negative breast cancer patients with homologous recombination deficiency and without germline mutations in BRCA1/2: The NOBROLA phase 2 study. (PubMed, Breast)
    The observed results could prompt further investigation.
    Clinical • P2 data • Journal • BRCA Biomarker • PARP Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
    |
    Lynparza (olaparib)
    1year
    Discovery of Pyrazolo[1,5,4-de]quinoxalin-2(3H)-one Derivatives as Highly Potent and Selective PARP1 Inhibitors. (PubMed, J Med Chem)
    30 achieved tumor regression in the BRCA1-mutated MDA-MB-436 xenograft model and showed synergistic efficacy in combination with carboplatin in the SUM149PT xenograft model. In the rat hematological toxicity study, 30 exhibited minimal impact on hematological parameters at 25 mg/kg, while AZD5305 at 1 mg/kg caused 56.5% reduction of reticulocyte. Taken together, we discovered compound 30 with a therapeutic index superior to that of PARP1 inhibitors AZD5305 and AZD9574 in the preclinical setting.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    |
    BRCA1 mutation • HRD • HRD + BRCA1 mutation
    |
    carboplatin • saruparib (AZD5305) • AZD9574
    1year
    A Comprehensive Genomic Profiling Solution That Integrates BRCA1/2 Mutational Status and Genomic Instability to Characterize Homologous Recombination Deficiency (AMP 2024)
    We developed a novel method to determine genomic instability for characterizing the consequences of HRD using OCA Plus, which was developed using CGP of cancer FFPE samples to aid research into precision oncology. By combining genomic instability assessment with DNA repair pathway analysis such as mutations in BRCA1/2 and other genes in HRR pathway, OCA Plus will support research into the mechanisms underlying HRD.
    BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
    |
    Oncomine™ Comprehensive Assay Plus
    1year
    Prevalence of actionable genomic alterations (GA) and predictive value of tumor mutational burden (TMB) for immune checkpoint inhibitor (ICI) effectiveness in HR(+)HER2(-) metastatic breast cancer (MBC) (SABCS 2024)
    Background: Pembrolizumab, an anti-PD1 antibody ICI is an FDA-approved option for patients with HR(+)HER2(-) MBC who have exhausted standard of care options and have high TMB (≥10 mut/mb, FoundationOne®CDx)... About 70% of TBx harbor at least one GA with established clinical utility. Pts with TMB10+ vs. TMB<10 had more favorable PFS and rwOS on ICI.
    Checkpoint inhibition • Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation • AKT1 mutation • HRD signature • BRCA1 fusion
    |
    FoundationOne® CDx
    |
    Keytruda (pembrolizumab)
    1year
    Pan-cancer Analysis of Homologous Recombination Deficiency in Cell Lines. (PubMed, Cancer Res Commun)
    We found that in cell lines, HRD was associated with sensitivity to PARP inhibition in breast cancer, but not at a pan-cancer level. By generating large-scale, pan-cancer datasets on HRD predictions in cell lines, we aim to facilitate efforts to improve our understanding of HRD and its utility as a biomarker.
    Preclinical • Journal • BRCA Biomarker • PARP Biomarker • Pan tumor
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type • HRD + BRCA1 mutation
    1year
    The discrepancy of somatic BRCA1/2 pathogenic variants from two different platforms in epithelial ovarian, fallopian tube, and peritoneal cancer. (PubMed, Sci Rep)
    In the case of the strong implication of BRCA PV/LPV with a negative result with one genetic test, different platforms could be considered in limited cases. Careful interpretation and further studies for the cross-validation of gene analysis platforms are needed.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA1 mutation + BRCA2 mutation
    1year
    The association of the chemotherapy response score and homologous recombination deficiency in patients undergoing interval tumor reductive surgery following neoadjuvant chemotherapy. (PubMed, Int J Gynecol Cancer)
    A positive response to chemotherapy at the time of interval tumor reductive surgery defined by the chemotherapy response score was associated with homologous recombination status and the likelihood of achieving a complete gross resection.
    Journal • BRCA Biomarker • Surgery
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation