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    GENE:

    BRCA1 (Breast cancer 1, early onset)

    i
    Other names: BRCA1, BRCC1, PPP1R53, RNF53, Breast cancer 1, early onset
    1d
    BRCA1: An Unrecognized Modulator of Lineage Plasticity in Basal-like Breast Cancer. (PubMed, J Mammary Gland Biol Neoplasia)
    Understanding the mechanisms underlying BRCA1-mediated lineage plasticity offers novel therapeutic avenues to target early-stage tumor initiation and progression in BRCA1-mutated breast cancer. This review perspective sheds light on the role of BRCA1 in lineage plasticity and highlights probable mechanisms by which BRCA1 could promote this lineage plasticity.
    Review • Journal • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset)
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    HER-2 expression
    1d
    A phase Ib study of sapacitabine and olaparib in patients with BRCA1/2-mutated metastatic breast cancer. (PubMed, Clin Cancer Res)
    Sapacitabine with olaparib produces high rates of hematologic toxicity. However, the ORR of 50%, mPFS of 9.7 months, and durability of response in some patients suggest possible combinatorial benefit. Further exploration of olaparib with different sapacitabine schedules or substitution of a PARP1-selective inhibitor to potentially decrease hematological toxicity is warranted.
    P1 data • Journal • BRCA Biomarker • PARP Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HER-2 negative • BRCA mutation
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    Lynparza (olaparib) • sapacitabine (CYC682)
    2d
    MutAnt: mutation annotation tool predicts deleteriousness of missense mutations and improves mutation calling from transcriptomics. (PubMed, Hum Genet)
    Moreover, MutAnt prediction scores of deleteriousness improved somatic variant calling from RNA sequencing data compared to standard approaches. MutAnt's high performance in distinguishing neutral and protein-disrupting mutations highlights its potential clinical utility in variant classification.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog)
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    TP53 mutation • PTEN mutation
    3d
    Sentinel Lymph Node Biopsy for Prophylactic Mastectomy: Necessary Precaution or Unnecessary Procedure? (PubMed, Ann Surg Oncol)
    Occult malignancy was uncommon, and SLNB positivity was exceedingly rare in prophylactic NSMs. Routine SLNB is not justified in this setting and should be reserved for select higher-risk scenarios. Personalized, risk-adapted approaches to axillary management and preoperative imaging are warranted.
    Journal
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
    3d
    NIRADO: Basket Trial Exploring the Efficacy and Safety of the Combination of Niraparib and Dostarlimab (clinicaltrials.gov)
    P2, N=51, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Dec 2027 --> Feb 2025 | Suspended --> Terminated; Abandon of the partner, GSK
    Trial completion date • Trial termination • Pan tumor • Platinum sensitive
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    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • CDK12 (Cyclin dependent kinase 12) • 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) • RAD51D (RAD51 paralog D) • ARID2 (AT-Rich Interaction Domain 2) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
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    HER-2 positive • HER-2 amplification • DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    4d
    ARIANES: Efficacy and Safety of the Combination of Rucaparib (PARP Inhibitor) and Atezolizumab (Anti-PD-L1 Antibody) in Patients With DNA Repair-deficient or Platinum-sensitive Solid Tumors (clinicaltrials.gov)
    P2, N=130, Terminated, Gustave Roussy, Cancer Campus, Grand Paris | Suspended --> Terminated; Bankruptcy of partner: Clovis
    Trial termination • Pan tumor • Platinum sensitive
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • 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) • IL2 (Interleukin 2) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • DRD (DNA Repair Deficiency)
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    DDR • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
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    Tecentriq (atezolizumab) • Rubraca (rucaparib)
    4d
    Comprehensive genomic profiling for homologous recombination deficiency guides PARP inhibitor therapy recommendations in ovarian cancer. (PubMed, Pathol Oncol Res)
    PARPi selection differed by HRD status, with niraparib favored in HR-proficient and olaparib in HRD-positive tumors. No additional profiling was required for PARPi therapy recommendation, and no incidental findings beyond the scope of HRD testing were detected. Molecular profiling with F1CDx proved to be a technically feasible, clinically impactful, and time-efficient assay, demonstrating its value in supporting molecular-guided PARPi therapy recommendations in the routine care of HGSOC patients.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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    HRD • BRCA mutation
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    FoundationOne® CDx
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    Lynparza (olaparib) • Zejula (niraparib)
    4d
    Switching from Zoledronic Acid to Denosumab for Bone Modification Therapy in Patients with Malignant Tumors and Renal Insufficiency: A Retrospective Case Series and Literature Review. (PubMed, Case Rep Oncol)
    Patients with abnormal renal function, BRCA1 mutations, or those at high risk of developing skeletal-related events may benefit from denosumab over zoledronic acid. During denosumab treatment in patients with renal dysfunction, attention should be paid to the occurrence of hypocalcemia.
    Retrospective data • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset)
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    Prolia (denosumab) • zoledronic acid
    4d
    A Case of Uterine Serous Carcinoma in a Patient with a Germline BRCA1 Mutation: Genomic Profiling Reveals an Ovarian Cancer-Like Molecular Signature. (PubMed, Case Rep Oncol)
    This finding suggests that BRCA1-associated USC may be sensitive to poly ADP-ribose polymerase inhibitors, and also raises the question of whether risk-reducing hysterectomy should be considered for patients with BRCA1 mutation. USC with a BRCA1 mutation may have molecular characteristics distinct from those of sporadic USC, and further accumulation and analysis of such cases are needed to evaluate the clinical implications.
    Journal • BRCA Biomarker • PARP Biomarker
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    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • RB1 (RB Transcriptional Corepressor 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1)
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    TP53 mutation • PIK3CA mutation
    5d
    RAD51B-EZH2 axis as a potential therapeutic target for TNBC through cell fate conversion. (PubMed, Cell Death Dis)
    Inhibition of the RAD51B-EZH2 axis allows the re-expression of functional ERα, making TNBC targetable by endocrine therapy. Consistently, the combination of EZH2 inhibitor with tamoxifen effectively reduces TNBC progression, suggesting that the RAD51B-EZH2 axis is a potential therapeutic target for TNBC.
    Journal • BRCA Biomarker
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    ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • RAD51B (RAD51 Paralog B)
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    FGFR2 mutation
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    tamoxifen
    5d
    Functional analysis of BRCA1 and BRCA2 splicing variants using a minigene assay. (PubMed, Hum Genomics)
    Finally aberrant splicing patterns were found in three of the four variants: BRCA1:c.80 + 3_80 + 5del, BRCA1:c.548-15G > A, BRCA2:c.8755-19 A > G that were previously classified as VUS through experimental analysis. As a result, we reclassify BRCA1;c.80 + 3_80 + 5del as LP and we classify BRCA1;c.548-15G > A and BRCA2;c.8755-19 A > G as VUS.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)