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    GENE:

    BRCA1 (Breast cancer 1, early onset)

    i
    Other names: BRCA1, BRCC1, PPP1R53, RNF53, Breast cancer 1, early onset
    1d
    Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)
    4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.
    Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
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    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion
    |
    FoundationOne® CDx
    |
    Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)
    1d
    Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
    Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
    Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    1d
    Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)
    HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.
    Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)
    |
    BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type
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    Myriad myChoice® CDx
    1d
    Homologous recombination (HR) and DNA damage repair (DDR) somatic alterations in metastatic colorectal cancer (mCRC): results from the comprehensive genomic profiling (CGP) trial FPG500 (AIOM 2024)
    Background : Treatment (tx) of MSS/MMRp mCRC relies mainly on oxaliplatin (oxa)- or irinotecan-based doublet chemotherapy regimens, with no biomarker reported so far, allowing the selection of one tx over the other. HR-DDRa is associated with MSI-H or TMB-H. Pts with MSS HR-DDRa tumors benefit from oxa-based first line treatment. Longer FU, allowing mature OS data, and wider cohorts are warranted.
    Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Metastases
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    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)
    |
    TMB-H • MSI-H/dMMR
    |
    TruSight Oncology 500 Assay
    |
    oxaliplatin • irinotecan
    1d
    Germline Genetic Susceptibility Testing Among Emirati Nationals at Risk for Hereditary Breast and Ovarian Cancer Syndrome. (PubMed, JCO Glob Oncol)
    A higher rate of P/LP variants is seen among Emirati patients at risk for hereditary breast and ovarian cancer syndrome compared with reports of similar patients from Western populations. Efforts to increase utilization and awareness of germline genetic testing are warranted among Emirati patients.
    Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    1d
    Estrogens and breast cancer. (PubMed, Ann Oncol)
    Yet emerging clinical and experimental evidence points to progestogens (endogenous progesterone or synthetic progesterone [progestin]) as the primary hormonal driver underlying seemingly estrogen-associated breast cancer risk...Estrogen HRT has shown an array of proven benefits, including ameliorating menopausal symptoms and improving bone health. Collective evidence thus suggests that estrogen HRT is likely to offer health benefits to perimenopausal or postmenopausal women, including breast cancer survivors, as well as young BRCA1/2 carriers with prophylactic oophorectomy for ovarian cancer prevention.
    Review • Journal
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    2d
    Advantages of next-generation sequencing (NGS) in the molecular classifi cation of endometrial carcinomas - our experience with 270 cases. (PubMed, Ceska Gynekol)
    In comparison with recommended diagnostic algorithms, NGS provides a more reliable classification of EC into particular molecular subgroups. Furthermore, NGS reveals the complex molecular genetic background in individual ECs, which is especially significant within ECs with no specific molecular profile. These data can serve as a springboard for the research of therapeutic programs committed to targeted therapy in this type of tumor.
    Journal • Next-generation sequencing • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • PMS2 (PMS1 protein homolog 2) • BCOR (BCL6 Corepressor) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • POLD1 (DNA Polymerase Delta 1)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • POLE mutation
    2d
    Adverse events in the placebo arm of SOLO2/ENGOT-Ov21 maintenance trial of olaparib in recurrent ovarian cancer. (PubMed, Gynecol Oncol)
    Virtually all PSROC participants in the SOLO2/ENGOT-Ov21 experienced one or more AE whilst on placebo. Furthermore, study investigators attributed one quarter of AEs to be related to placebo therapy and dose alterations and treatment changes were made based on these AE. Further work is needed to improve measurement and categorization of AEs in trials of maintenance therapy in PSROC.
    Journal • Adverse events • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    BRCA2 mutation • BRCA1 mutation
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    Lynparza (olaparib)
    2d
    PARylation of GCN5 by PARP1 mediates its recruitment to DSBs and facilitates both HR and NHEJ Repair. (PubMed, Cell Mol Life Sci)
    Together, this study identifies an untraversed DSB repair function of GCN5 and provides mechanistic insights into transcriptional as well as post-translational regulation of pivotal HR-NHEJ factors. Alongside, it highlights the translational importance of PARP1-GCN5 axis in mediating GBM radio-resistance.
    Journal
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    BRCA1 (Breast cancer 1, early onset) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • PRKDC (Protein Kinase, DNA-Activated, Catalytic Subunit) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
    2d
    BRCA1 and BRCA2: from cancer susceptibility to synthetic lethality. (PubMed, Genes Dev)
    Additionally, we discuss current preventive measures for BRCA1/2 mutation carriers and targeted treatment options based on the concept of synthetic lethality. Finally, we explore the challenges of acquired therapy resistance and discuss potential alternative avenues for targeting BRCA1/2 mutant tumors.
    Review • Journal • BRCA Biomarker • Synthetic lethality
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    BRCA2 mutation • BRCA1 mutation
    2d
    Effects of BRCA1 overexpression via the NRF2 / HO1 / NQO1 pathway on oral cancer cells proliferation, migration, and apoptosis. (PubMed, Heliyon)
    Experiments involving oral cancer cells confirmed that BRCA1 overexpression could up-regulate the NRF2 signalling pathway, reduce oxidative damage, and inhibit cell proliferation and other biological behaviours. The BRCA1 and NRF2 pathways might be associated with oral cancer occurrence and development.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • NQO1 (NAD(P)H dehydrogenase, quinone 1)
    |
    BRCA1 expression
    3d
    Prevalence of BRCA1 and BRCA2 mutations in ovarian cancer patients from Yunnan Province in southwest China. (PubMed, Eur J Cancer Prev)
    The prevalence and spectrum of BRCAm in OC patients from Yunnan Province are different from those in other groups. BRCA status testing is advised for all OC patients, particularly those with a family history of HBOC.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
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    BRCA2 mutation • BRCA1 mutation • BRCA1 mutation + BRCA2 mutation
    3d
    Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast. (PubMed, Clin Cancer Res)
    The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    3d
    Gestational breast cancer: distinctive molecular and clinico-epidemiological features. (PubMed, J Mammary Gland Biol Neoplasia)
    Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.
    Observational data • Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    BRCA2 mutation • BRCA1 mutation
    3d
    Redefining pancreatic cancer management with tumor-agnostic precision medicine. (PubMed, Carcinogenesis)
    Despite the rarity of NTRK fusions in pancreatic cancer, larotrectinib and entrectinib have exhibited effectiveness in NTRK fusion-positive pancreatic cancers. Additionally, repotrectinib, a next-generation NTRK inhibitor, has shown promising activity in NTRK positive pancreatic cancer patients who have developed acquired resistance to previous NTRK inhibitors. Immune checkpoint inhibitors, such as pembrolizumab and dostarlimab, have proven to be effective in dMMR/MSI-H pancreatic cancers...It is crucial to continue implementing comprehensive screening strategies that encompass the ability to detect all these tumor-agnostic biomarkers. This will be essential in identifying pancreatic cancer patients who may benefit from these therapies.
    Journal • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Pan tumor
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • MSI-H/dMMR • KRAS G12C • HER-2 overexpression • BRAF mutation • BRAF V600 • RET fusion • FGFR2 mutation • FGFR2 fusion • ALK fusion • NRG1 fusion • KRAS G12 • NTRK positive • NTRK fusion
    |
    Keytruda (pembrolizumab) • Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Jemperli (dostarlimab-gxly) • Augtyro (repotrectinib)
    3d
    An overview about biomarkers in breast cancer: Insights into the diagnostic and prognostic significance. (PubMed, Clin Chim Acta)
    Biomarker targets must undergo experimental and clinical trials on samples of significant size before reaching clinical utility. In this review, we compile the classical markers and describe the potential use of other markers associated with the biological processes of this neoplasm.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    3d
    Real-World Evidence on Prescribing Patterns and Clinical Outcomes of Metastatic Breast Cancer Patients Treated with PARP Inhibitors: The Mayo Clinic Experience. (PubMed, Clin Breast Cancer)
    In real-world practice, PARPis are well-tolerated with promising TTF in gBRCA1/2 and gPALB2 carriers. Further studies will delineate the clinical efficacy of PARPis in other MBC subsets, such as sBRCA mutations, HER2-positive disease, and CNS metastasis.
    Clinical data • Journal • HEOR • Real-world evidence • BRCA Biomarker • PARP Biomarker • Real-world • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
    |
    HER-2 positive
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    Lynparza (olaparib) • Talzenna (talazoparib)
    3d
    Commentary: Why is genetic testing underutilized worldwide? The case for hereditary breast cancer. (PubMed, BJC Rep)
    We discuss how these factors may lead to the underutilization of genetic testing in North America and throughout the world and discuss alternative models of genetic healthcare delivery. We have invited leaders in cancer genetic from around the world to tell us what they think are the barriers to testing in their host countries.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    3d
    Molecular Alterations in Paired Epithelial Ovarian Tumors in Patients Treated with Neoadjuvant Chemotherapy. (PubMed, Cancers (Basel))
    This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.
    Journal • Tumor mutational burden • BRCA Biomarker
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    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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    BRCA2 mutation • BRCA1 mutation • HRD
    3d
    How Psychophysical Stress Can Mediate the Effects of Anxiety and Depression on the Overall Quality of Life and Well-Being in Women Undergoing Hereditary Breast Cancer Screening. (PubMed, Cancers (Basel))
    These findings indicate that addressing both anxiety and depression in genetic counseling is crucial for enhancing mental and overall well-being. Interventions should focus on stress management to improve the quality of life, emphasizing depression treatment to enhance physical health outcomes.
    Journal • HEOR • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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    BRCA2 mutation • BRCA1 mutation
    3d
    Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer. (PubMed, Nat Genet)
    Transcription factor analyses identify loss of ELF5 and gain of AP-1 sites in these epigenetically primed regions; in vivo experiments further implicate AP-1 and Wnt10a as strong promoters of Brca1-related breast cancer. These findings reveal a previously unappreciated epigenetic effect of Brca1 haploinsufficiency in accelerating tumorigenesis, advancing our mechanistic understanding and informing potential therapeutic strategies.
    Preclinical • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • ELF5 (E74 Like ETS Transcription Factor 5)
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    BRCA1 mutation
    3d
    BRCA2 and TP53 Mutations in a Breast Cancer Patient: A Case Report and Review of the Literature. (PubMed, Cureus)
    Multigene tests are essential in the treatment approach to young BC patients, since the detection of specific mutations may help guide changes in preventive measures and treatment plans. This report describes a rare case of BC in a young patient with pathogenic germline variants in BRCA2 and TP53 genes and also presents a literature review of the topic.
    Review • Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    |
    TP53 mutation • BRCA2 mutation + TP53 mutation
    3d
    Genomic alterations associated with early-stage disease and early recurrence in patients with colorectal cancer. (PubMed, Oncologist)
    Early-stage CRC patients can have distinct genomic profiles and CGP in this population can help expand access to targeted therapies.
    Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker
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    BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • RNF43 (Ring Finger Protein 43)
    |
    BRAF V600E • MSI-H/dMMR • BRAF V600 • RNF43 mutation
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    FoundationOne® CDx
    3d
    Metabolically inducing defects in DNA repair sensitizes BRCA-wild-type cancer cells to replication stress. (PubMed, Sci Signal)
    Small-molecule inhibition of mitochondrial respiration-using glyceollin I, metformin, or phenformin-induced overproduction of the oncometabolite lactate, which acidified the extracellular milieu and repressed the expression of homologous recombination (HR)-associated DNA repair genes...These effects were selective to breast cancer cells; normal epithelial cells retained HR proficiency and cell viability. These mechanistic insights into the BRCAness-prone properties of breast cancer cells support the therapeutic utility and cancer cell-specific potential of mitochondria-targeting drugs.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA1 mutation • BRCA wild-type
    |
    metformin
    5d
    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
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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    BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
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    Oncomine™ Comprehensive Assay Plus
    5d
    Evaluation of a Spike-in Method to Detect CNV Events Using Next-Generation Sequencing (NGS) Short-Read Technology (AMP 2024)
    We demonstrate the utility of an NGS standardization spike-in control to accurately detect large CNVs and exon level duplications greater than 2 exons. This approach reduces the minimum sequencing coverage required to appropriately measure these types of alterations, thus reducing the overall cost of sequencing. Additional work to increase sensitivity and lower IS input level will be discussed.
    Next-generation sequencing • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
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    TruSight Hereditary Cancer Panel
    5d
    The DNA Methylation Profiling Assay as a Powerful Tool in Classifying Carcinomas of Unknown Origin (AMP 2024)
    Here we describe an interesting case of donor-derived gynecologic origin tumor found in a liver transplant recipient. TUO classification by the Northwestern DNA methylation assay was critical in the following work-up to confirm site of origin of this tumor. This case demonstrates the robustness of the TUO classifier and its utility in identifying the tumor type in challenging cases, which is essential for appropriate treatment and clinical management.
    BRCA Biomarker • Epigenetic controller
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset)
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    TP53 mutation • BRCA1 mutation
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    PGDx elio™ tissue complete assay
    5d
    Comprehensive Evaluation of Copy Number Variation from Gene to Arm-Level Using Targeted Sequencing (AMP 2024)
    OCA Plus supports comprehensive detection of relevant copy number alterations in cancer FFPE samples. Combined with small variant profiling, detection of MSI, TMB, and HRD, OCA Plus facilitates comprehensive analysis of DNA structural changes in cancer that are relevant to precision oncology research.
    Tumor mutational burden • BRCA Biomarker
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    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HRD (Homologous Recombination Deficiency)
    |
    IDH1 mutation • HRD • IDH1 mutation + Chr del(1p) + Chr del(19q)
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    Oncomine™ Comprehensive Assay Plus
    5d
    The Use of Internal Controls in Next-Generation Sequencing to Improve BRCA1 and BRCA2 Gene Copy Loss Detection (AMP 2024)
    SNAQ-SEQ copy loss detection was based on estimating the exon abundance of ATM, BRCA1, BRCA2, and PALB2 genes, converting abundance into copies per cell and then detecting genes with significantly lower copy number. The CNV detection comparison between OCAv3 with and without SNAQ indicated that analysis with SNAQ was more robust, giving a result for every gene in every sample. Further, there were copy losses detected by OCAv3 that were not supported by SNAQ analysis.
    Next-generation sequencing • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    Oncomine™ Comprehensive Assay v3M
    5d
    Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)
    Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.
    Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • 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) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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    BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion
    |
    OncoExTra™ test
    5d
    Comparison of Ovarian Tumor Homologous Recombination Deficiency (HRD) Status Generated from the Illumina TruSight Oncology 500 (TSO500) High-Throughput HRD Assay to the Myriad myChoice CDx Assay (AMP 2024)
    The FDA (US Food and Drug Administration) has approved olaparib as a front-line maintenance therapy in combination with bevacizumab for patients with newly diagnosed advanced ovarian, fallopian tube, or primary peritoneal cancer with HRD+ status. We have demonstrated that the TSO500-HRD assay can accurately determine HRD status in ovarian tumors.
    BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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    BRCA2 mutation • BRCA1 mutation • HRD
    |
    Myriad myChoice® CDx • TruSight Oncology 500 Assay • TruSight Oncology 500 HRD Assay
    |
    Avastin (bevacizumab) • Lynparza (olaparib)
    5d
    Validation of a Homologous Recombination Deficiency (HRD) Assay for Use in Combination with Comprehensive Genomic Profiling (CGP) Testing (AMP 2024)
    The TruSight Oncology 500 comprehensive solid tumor next-generation sequencing panel with HRD assay demonstrated a high degree of sensitivity and specificity for deployment in a clinical setting.
    Combination therapy • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
    |
    HRD
    |
    Myriad myChoice® CDx • TruSight Oncology 500 Assay • TruSight Oncology 500 HRD Assay
    6d
    PLATPARP: A Trial of Niraparib in Platinum-Sensitive Castration-Resistant Prostate Cancer with DNA Repair Defects (clinicaltrials.gov)
    P2, N=12, Completed, Abramson Cancer Center at Penn Medicine | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024 | Trial primary completion date: Jun 2024 --> Feb 2024
    Trial completion • Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • HDAC2 (Histone deacetylase 2)
    |
    Zejula (niraparib)
    6d
    Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)
    P1, N=1, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024
    Trial completion • Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • BAP1 (BRCA1 Associated Protein 1) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2) • FANCC (FA Complementation Group C)
    |
    BRCA1 mutation • PALB2 mutation
    |
    MSK-IMPACT
    |
    cisplatin • gemcitabine
    7d
    Inhibiting ADAM17 enhances the efficacy of olaparib in ovarian cancer spheroids. (PubMed, Sci Rep)
    Using a 3D spheroid model from primary cells, we confirmed the 2D monoculture results and demonstrated not only increased caspase activity under the combined treatment but also a substantial gain in cytotoxicity compared to the mono-treatment. Our study proposes ADAM17 inhibition sensitizing ovarian cancer to olaparib treatment and improving treatment response.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • ADAM17 (ADAM Metallopeptidase Domain 17)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation
    |
    Lynparza (olaparib)
    10d
    Paxalisib Plus Olaparib or Pembrolizumab/Chemotherapy in Advanced Breast Cancer (ACTRN12624001340527)
    P1, N=24, Not yet recruiting, Kazia Therapeutics
    New P1 trial • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    HER-2 negative
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • carboplatin • albumin-bound paclitaxel • paxalisib (GDC-0084)
    10d
    Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, University of Washington | Trial primary completion date: Sep 2024 --> Dec 2025
    Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation
    |
    UW-Oncoplex™
    |
    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    10d
    TRIFOUR: Nadunolimab in Combination with Gemcitabine Plus Carboplatin in Patients with Advanced Triple Negative Breast Cancer. (clinicaltrials.gov)
    P1/2, N=116, Recruiting, Cantargia AB | Trial primary completion date: Aug 2026 --> Jun 2025
    Trial primary completion date • Combination therapy • BRCA Companion diagnostic • PARP Companion diagnostic • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • HER-2 negative + HR negative • HER-2 negative + HR negative + BRCA mutation
    |
    PD-L1 IHC 22C3 pharmDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    |
    carboplatin • gemcitabine • nadunolimab (CAN04)
    11d
    Establishment of a clinical cancer genetics program for breast cancer in a resource-limited country; challenges and opportunities. (PubMed, Front Oncol)
    In addition to its important role in preventing more cancers in index patients themselves and among their close relatives, identification of pathogenic or likely pathogenic variants, mostly in BRCA1 or BRCA2, may inform therapeutic decisions in common cancers including breast, ovarian, prostate and pancreatic cancers. In this manuscript, we describe the experience of a comprehensive cancer center, in a resource-limited country in establishing a comprehensive clinical cancer genetics program that can serve as an example for others who share similar demographic and financial restrains.
    Review • Journal
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    11d
    A Pilot Study on BRCA1/2 and PI3K Mutations Across Subtypes of Triple Negative Breast Cancer in North Indian Population. (PubMed, Appl Immunohistochem Mol Morphol)
    Considering high incidence of breast cancer and lack of correlation of basal morphology with BRCA1/2 mutation, the molecular methods should be used for screening for BRCA1/2 mutations. This will not only help in familial screening but also in deciding targeted therapy with PARP (poly-ADP ribose polymerase) inhibitors.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • VIM (Vimentin) • PI3K (Phosphoinositide 3-kinases)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation
    11d
    PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)
    P=N/A, N=1395, Recruiting, Beth Israel Deaconess Medical Center | N=500 --> 1395 | Trial completion date: Mar 2028 --> Dec 2032 | Trial primary completion date: Mar 2027 --> Dec 2032
    Enrollment change • Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation
    11d
    Breast Cancer Prognosis in Young BRCA1/BRCA2 Mutation Carriers: A Retrospective Hospital-based Cohort Study. (PubMed, Clin Oncol (R Coll Radiol))
    In this large hospital-based cohort of patients with very early-onset breast cancer, we found no clear evidence that gBRCA1/2m significantly affects OS after adjusting for known prognostic factors.
    Retrospective data • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • BRCA mutation