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    GENE:

    PALB2 (Partner and localizer of BRCA2)

    i
    Other names: PALB2, Partner And Localizer Of BRCA2, FANCN, Truncated Partner And Localizer Of BRCA2, Fanconi Anemia, Complementation Group N, Mutant Partner And Localizer Of BRCA2, PNCA3
    7d
    Familial and hereditary pancreatic cancer in Japan. (PubMed, Fam Cancer)
    The efficacy of olaparib maintenance therapy, as confirmed by the POLO study, has significantly impacted the clinical treatment of advanced PC patients in Japan. Since the initiation of precision cancer medicine in 2019, genetic medicine for PC patients has expanded in Japan.
    Review • Journal • BRCA Biomarker • PARP Biomarker • BRCA Companion diagnostic • PARP Companion diagnostic
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
    |
    Lynparza (olaparib)
    8d
    The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study. (PubMed, Cancers (Basel))
    The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
    10d
    Men with metastatic prostate cancer carrying a pathogenic germline variant in breast cancer genes: disclosure of genetic test results to relatives. (PubMed, Fam Cancer)
    Carriers felt motivated to disclose their genetic test result to relatives. Most of them indicated that the disclosure was not experienced as a psychological burden.
    Journal • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    11d
    Clinical actionability of BRCA2 alterations in uterine leiomyosarcoma: a molecular tumor board case report and a cBioPortal comprehensive analysis. (PubMed, Oncologist)
    uLMS displays a significant frequency of somatic BRCA2alt homDel. Considering their dismal prognosis, further investigation is warranted to test the use of PARPi in uLMS, and particularly in the setting of BRCA1/2 alterations.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C)
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    BRCA2 mutation
    |
    Zejula (niraparib)
    11d
    Assessing Clinical Features and Outcome of Breast Cancer in PALB2 Mutation Carriers: the Palbreast Study (clinicaltrials.gov)
    P=N/A, N=600, Recruiting, Azienda Ospedaliero-Universitaria di Modena
    New trial
    |
    PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
    19d
    CLINICAL AND BIOLOGICAL SIGNIFICANCE OF T-CELL RECEPTOR REPERTOIRE IN PATIENTS WITH BREAST CANCER (GBCC 2024)
    These results demonstrate that the TCR repertoire is associated with characteristics, genetic alterations, and clinical outcomes. Monitoring changes in the TCR repertoire may serve as a prognostic biomarker for breast cancer patients.
    Clinical • IO biomarker
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
    |
    PIK3CA mutation • PIK3CA H1047R • PTEN mutation • PALB2 mutation • PIK3CA H1047L • PIK3CA mutation + PTEN mutation
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    Oncomine™ Comprehensive Assay v3M • Oncomine™ TCR Beta-LR Assay
    19d
    Germline biallelic BRCA2 pathogenic variants and medulloblastoma: an international cohort study. (PubMed, J Hematol Oncol)
    In conclusion, MB in patients with biallelic BRCA2 pathogenic variants is a lethal disease. Future experimental treatments are necessary to help these patients.
    Journal • BRCA Biomarker
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    BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
    22d
    Role of Breast Cancer Risk Estimation Models to Identify Women Eligible for Genetic Testing and Risk-Reducing Surgery. (PubMed, Biomedicines)
    We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies.
    Review • Journal • BRCA Biomarker • Surgery
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • 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)
    25d
    Meta-analysis of breast cancer risk for individuals with PALB2 pathogenic variants. (PubMed, Genet Epidemiol)
    Pathogenic mutations in PALB2 makes women more susceptible to BC. Our risk estimates can help clinically manage patients carrying pathogenic variants in PALB2.
    Retrospective data • Journal
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    PALB2 (Partner and localizer of BRCA2)
    |
    PALB2 mutation
    26d
    Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico. (PubMed, JCO Glob Oncol)
    Despite the resource-constrained setting, relevant rates of RR measures and CT were observed. Targeted interventions to reduce out-of-pocket expenses and improve patient-physician communication and patients' understanding on carrier status are warranted to enhance the overall benefit of GCRA and ultimately improve the provision of patient-centered care to both carriers and their at-risk relatives.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C)
    1m
    Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy. (PubMed, Eur J Surg Oncol)
    Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    1m
    Association Between Polymorphisms in DNA Damage Repair Pathway Genes and Female Breast Cancer Risk. (PubMed, DNA Cell Biol)
    Stratified analysis revealed that PALB2 rs16940342 increased breast cancer risk in response to menstrual status (AG/GG vs. AA: adjusted OR = 1.72, 95%CI: 1.13-2.62, p = 0.011) and age of menarche (AG/GG vs. AA: adjusted OR = 1.54, 95%CI: 1.03-2.31, p = 0.037), whereas ATM rs611646 and Ku70 rs132793 were associated with reduced breast cancer risk influenced by menarche (GA/AA vs. GG: adjusted OR = 0.50, 95%CI: 0.30-0.95, p = 0.033). In a summary, PALB2 rs16940342, ATR rs13091637, ATM rs611646, and Ku70 rs132793 were associated with breast cancer risk.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PALB2 (Partner and localizer of BRCA2)
    |
    HER-2 expression • ER expression
    1m
    PALB2-mutated human mammary cells display a broad spectrum of morphological and functional abnormalities induced by increased TGFβ signaling. (PubMed, Cell Mol Life Sci)
    KRT14-positive cells are also more abundant with DNA damage than KRT14-negative cells. The obtained results indicate comprehensive cellular changes upon PALB2 mutations, even in the presence of half dosage of wild type PALB2 and demonstrate how PALB2 mutations may predispose their carriers to malignancy.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • KRT14 (Keratin 14)
    |
    BRCA1 mutation • PALB2 mutation
    1m
    Immunohistochemical Findings and Clinicopathological Features of Breast Cancers with Pathogenic Germline Mutations in Non-BRCA Genes. (PubMed, Hum Pathol)
    With PTEN and CHEK2 pathogenic mutations, abnormal IHC patterns are seen in early atypical proliferative lesions. IHC may be applied to identify CHEK2 &PTEN mutated BCs and precursor lesions.
    Journal • BRCA Biomarker
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    PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
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    ATM mutation • PTEN deletion • PTEN mutation • PALB2 mutation • CHEK2 mutation • ATM expression
    1m
    Generation and characterization of the iPS cell line (SYSUSHi001-A) derived from the peripheral blood mononuclear cells (PBMCs) of a 33-year-old patient with acute myeloid leukemia (AML). (PubMed, Stem Cell Res)
    This iPSC line was facilitated through the use of episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, and human miR-302. The SYSUSHi001-A iPSC line exhibited characteristic embryonic stem cell-like morphology, maintained the XPO1 and PALB2 mutations, expressed key pluripotency markers, preserved a normal karyotype (46, XY), and demonstrated the ability to differentiate into cells from all three germ layers in vitro.
    Preclinical • Journal • IO biomarker
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    PALB2 (Partner and localizer of BRCA2) • KLF4 (Kruppel-like factor 4) • SOX2 • XPO1 (Exportin 1) • POU5F1 (POU Class 5 Homeobox 1)
    |
    PALB2 mutation • XPO1 mutation
    2ms
    Genetic analysis of PALB2 gene WD40 domain in canine mammary tumour patients. (PubMed, Vet Med Sci)
    The current project is the first study investigating the relationship between the PALB2 gene WD40 domain and CMTs. Our findings will contribute to a better understanding of the pathogenic mechanism of the PALB2 gene in CMTs. In humans, variant positions in canines have been linked to cancer-related phenotypes such as familial BC, endometrial tumor, and hereditary cancer predisposition syndrome. The results of bioinformatics analyses should be investigated through functional tests or case-control studies.
    Journal
    |
    PALB2 (Partner and localizer of BRCA2)
    |
    PALB2 mutation
    2ms
    Two Germline Pathogenic Variants in Cancer Susceptibility Genes and Their Null Implication in Breast Cancer Pathogenesis: The Importance of Tumoral Homologous Recombination Deficiency Testing. (PubMed, JCO Precis Oncol)
    Homologous recombination proficiency in patients with breast cancer despite germline PALB2/RAD51C pathogenic variants.
    Journal
    |
    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C)
    |
    HRD
    2ms
    PARP Inhibitors for Breast Cancer Treatment: A Review. (PubMed, JAMA Oncol)
    Future research should focus on identifying predictive biomarkers and therapeutic strategies to overcome resistance. Integrating well-designed translational efforts into all clinical studies is thereby crucial to laying the groundwork for future insights from ongoing research.
    Review • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • PARP2 (Poly(ADP-Ribose) Polymerase 2)
    2ms
    Family health beliefs and cascade genetic testing in Asian families with hereditary cancer risk: "Okay, now what?". (PubMed, J Genet Couns)
    This study represents an important contribution to the literature about cascade testing among an underrepresented group. Shared family health beliefs about genetic testing may be particularly relevant for this community and these findings can inform strategies to increase cascade genetic testing in Asian families.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    2ms
    Pleomorphic/solid lobular carcinoma of male breast with PALB2 germline mutation: case report and literature review. (PubMed, Pathologica)
    Here, we report a rare and interesting case of an invasive pleomorphic/solid lobular carcinoma, which carries a pathogenic variant in PALB2 gene, and a family history of breast cancer without other well defined risk factors for developing this type of neoplasia. In addition, we review the current literature.
    Clinical • Clinical protocol • Observational data • Retrospective data • Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    BRCA2 mutation • PALB2 mutation
    2ms
    Retrospective genetic testing (Traceback) in women with early-onset breast cancer after revised national guidelines: a clinical implementation study. (PubMed, Breast Cancer Res Treat)
    The insights from the participants' perspectives and sentiments throughout the process support the notion that the Traceback procedure is a safe and an appreciated complement to routine genetic counseling. The genetic yield of almost 10% also suggests that the associated extra workload for genetic counselors could be viewed as acceptable in clinical implementation scenarios.
    Retrospective data • 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) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    2ms
    Pancreatic cancer biomarkers: A pathway to advance in personalized treatment selection. (PubMed, Cancer Treat Rev)
    Consequently, there has been a growing interest in biomarkers that may help guide targeted therapy in pancreatic cancer. Therefore, this review aims to offer an updated perspective on biomarkers with therapeutic potential in pancreatic cancer.
    Review • Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • IO biomarker
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    KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NRG1 (Neuregulin 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • MSI-H/dMMR • KRAS G12C • PALB2 mutation • NRG1 fusion • KRAS G12
    2ms
    Characterizing PALB2 intragenic duplication breakpoints in a triple-negative breast cancer case using long-read sequencing. (PubMed, Front Oncol)
    Using our combined methodology, we reclassified the PALB2 duplication as a pathogenic variant. This reclassification suggests a possible causative link between this specific genetic alteration and the aggressive phenotype of the patient.
    Journal
    |
    PALB2 (Partner and localizer of BRCA2)
    2ms
    Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management. (PubMed, Urol Oncol)
    Evidence suggests abiraterone may be superior to docetaxel as a first-line treatment for patients with IDC-P. To address these and other critical pathological attributes, this review examines the molecular pathology, genetics, treatments, and oncologic outcomes associated with CC-P, PDA, and IDC-P with the objective of creating a comprehensive resource with a centralized repository of information on PDA, IDC-P, and CC-P.
    Review • Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • RB1 (RB Transcriptional Corepressor 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7) • NKX3-1 (NK3 homeobox 1)
    |
    TP53 mutation • PTEN mutation • PALB2 mutation • CHEK2 mutation
    |
    docetaxel • abiraterone acetate
    2ms
    Efficacy of Poly(ADP-ribose) Polymerase Inhibitors by Individual Genes in Homologous Recombination Repair Gene-Mutated Metastatic Castration-Resistant Prostate Cancer: A US Food and Drug Administration Pooled Analysis. (PubMed, J Clin Oncol)
    In this pooled analysis, benefit from PARPi appeared greatest for patients with BRCA1m, BRCA2m, CDK12m, and PALB2m. Given limitations of this exploratory analysis, the apparent lack of benefit from PARPi in patients with CHEK2m or ATMm should be further explored in future clinical trials.
    Retrospective data • Journal • BRCA Biomarker • PARP Biomarker • Metastases
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    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12)
    2ms
    Whole exome sequencing of a novel homozygous missense variant in PALB2 gene leading to Fanconi anaemia complementation group. (PubMed, Biomed Rep)
    The results support the role of PALB2 gene and pathogenic variants that may cause clinical presentation of FA. Furthermore, the present results may establish a disease database, providing a groundwork for understanding the key genomic regions to control diseases resulting from consanguinity.
    Journal • BRCA Biomarker
    |
    BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    PALB2 mutation
    2ms
    A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate Cancer Demonstrating "BRCAness" Genotype (ROAR). (PubMed, Oncologist)
    Rucaparib demonstrated acceptable toxicity and efficacy signal as an ADT-sparing approach in patients with biochemically recurrent nonmetastatic prostate cancer. It is currently challenging to understand the optimal value of systemic therapy in this disease setting due to the rapidly changing standard of care. Additionally, there are relatively few patients with BRCAness who present with nonmetastatic hormone-sensitive prostate cancer (ClinicalTrials.gov Identifier: NCT03533946).
    P2 data • Journal • BRCA Biomarker • PARP Biomarker • Metastases
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)
    |
    ATM mutation • PALB2 mutation • CHEK2 mutation • RAD51 mutation
    |
    Rubraca (rucaparib)
    2ms
    Incidence of pathogenic germline variants and presumed germline pathogenic variants in Japanese lung cancer patients using comprehensive genomic profiling tests (AACR 2024)
    The incidence of PGV in NOP and PGPV in F1L and F1CDx were 4/321 (1.2%), 36/773 (4.7%), and 141/2145 (6.6%), respectively (NOP vs F1L vs F1CDx; p = 0.001 NOP vs F1L; p = 0.006, NOP vs F1CDx; p < 0.001, F1L vs F1CDx; p=0.190). The 4 PGVs detected by NOP were in the ATM, BRCA2, MSH6, and TP53 genes. Notably, two out of four patients were in their 30s while the other two were in their 70s.
    Clinical • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2)
    |
    FoundationOne® CDx • FoundationOne® Liquid CDx • OncoGuide™ NCC Oncopanel System
    3ms
    Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women. (PubMed, J Clin Oncol)
    Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness.
    Journal
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    PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    3ms
    Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes. (PubMed, Ann Oncol)
    Worse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.
    Journal • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • HDAC2 (Histone deacetylase 2)
    |
    BRCA2 mutation • BRCA1 mutation
    3ms
    A Somatic BRCA2-Mutated Pancreatic Adenocarcinoma With Sustained Exceptional Response to Modified FOLFIRINOX. (PubMed, Oncologist)
    Patients with HRR deficiency-associated gene mutations such as BRCA1, BRCA2, and PALB2 are more susceptible to platinum-based chemotherapies and in those with somatic BRCA mutations, PARP inhibitor therapy prolongs progression-free survival. The case discussed herein illustrates the therapeutic opportunities offered through the identification of HRR deficiency in pancreatic cancer, as well as the challenges associated with treatment and prevention of central nervous system metastases in long-term survivors of pancreatic cancer.
    Journal • BRCA Biomarker • PARP Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRCA mutation • PARP1 mutation
    |
    5-fluorouracil • irinotecan • leucovorin calcium
    3ms
    Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan. (PubMed, J Biomed Sci)
    Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.
    Clinical • Clinical data • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • FANCC (FA Complementation Group C)
    |
    BRCA1 mutation • ATM mutation • PALB2 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • FANCA mutation • BLM mutation • NBN mutation
    3ms
    Homologous Recombination Repair Defects in Metastatic vs Primary Acinar Prostatic Adenocarcinoma (USCAP 2024)
    The frequency of Tier 1/2 HRD in metastatic PC is twice that of primary PC (p=0.001). No association was identified between CC/IDC morphology and HRD in primary cases, or between HRD and site of metastases. Additional work exploring less frequent HR genes in primary and metastatic PC is ongoing.
    PARP Biomarker • BRCA Biomarker • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
    |
    HRD
    |
    Oncomine™ Comprehensive Assay v3M
    3ms
    Cost-Effectiveness of Population-Based Multigene Testing for Breast and Ovarian Cancer Prevention. (PubMed, JAMA Netw Open)
    In this economic analysis of population-based multigene testing, population-based testing was a more cost-effective strategy for the prevention of breast cancer and ovarian cancer when compared with the current family history-based testing strategy at the $100 000 per QALY willingness-to-pay threshold. These findings support the need for more comprehensive genetic testing strategies to identify pathogenic variant carriers and enable informed decision-making for personalized risk management.
    Journal • HEOR • BRCA Biomarker • Cost-effectiveness • Cost effectiveness
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
    3ms
    Gender-Specific Genetic Predisposition to Breast Cancer: BRCA Genes and Beyond. (PubMed, Cancers (Basel))
    Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.
    Review • 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) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2)
    3ms
    Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer. (PubMed, JAMA Netw Open)
    CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.
    Journal • HEOR • Cost-effectiveness • Cost effectiveness
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    tamoxifen • anastrozole
    3ms
    Population Estimates of Ovarian Cancer Risk in a Cohort of Patients with Bladder Cancer. (PubMed, Eur Urol Focus)
    This study provides evidence against routine oophorectomy for reducing OC risk in females with BC. The results highlight that the development of OC occurred 11 yr before diagnosis of BC for patients with OC mutations and 15 yr before diagnosis of BC for patients without OC mutations.
    Journal
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    PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
    |
    PALB2 mutation
    3ms
    Targeting BRCA and PALB2 in Pancreatic Cancer. (PubMed, Curr Treat Options Oncol)
    Identifying which patients are more prone to certain mechanisms of resistance and tackling them with specific treatment strategies are areas of active investigation. Additionally, given that PARP inhibitors have limited overall efficacy for most patients, upfront combination strategies are an important future strategy.
    Review • Journal • BRCA Biomarker • PARP Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
    4ms
    Characterization of Epithelial Ovarian Cancer Based on Multi-Gene Tumour Testing and Homologous RecomBinatiOn Deficiency (HRD) Testing (COMBO) (SGO 2024)
    Multi-gene NGS tumour testing was capable of identifying all clinically relevant germline variants. Although paired multi-gene tumour-germline testing is required to determine variant origin, over 40% of individuals in this study could have avoided germline testing following negative tumour results. These results suggest that streamlining genetic testing for EOC patients via primary multi-gene tumour testing is possible with further investigation.
    PARP Biomarker • 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) • STK11 (Serine/threonine kinase 11) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1)
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    HRD
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    Myriad myChoice® CDx
    4ms
    Histologic patterns in prostatic adenocarcinoma are not predictive of mutations in the homologous recombination repair pathway. (PubMed, Hum Pathol)
    Tumors with >20  % or >30  % histologic patterns by volume also demonstrated no significant association with mutational status. This study suggests that histopathologic examination alone is insufficient to distinguish prostate cancer with germline or somatic mutations in HRR pathway genes, highlighting the continuing importance of ancillary molecular diagnostics in guiding therapy selection for prostate cancer patients who may benefit from PARP inhibitors.
    Journal • BRCA Biomarker • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • 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)) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • ABRAXAS1 (Abraxas 1 BRCA1 A Complex Subunit 2)
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    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 expression
    4ms
    The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers. (PubMed, Genes (Basel))
    We also found that the mutational spectrum of post-chemotherapy tumors was more reflective of matching metastatic tumor biopsies than pre-chemotherapy samples. These findings support a portrait of modest ongoing genomic instability with respect to single-nucleotide variants induced by or selected for by chemotherapy in TNBCs.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • APOBEC3B (Apolipoprotein B MRNA Editing Enzyme Catalytic Subunit 3B) • XRCC3 (X-Ray Repair Cross Complementing 3)
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    TP53 mutation • PALB2 mutation
    4ms
    Counselling Framework for Germline BRCA1/2 and PALB2 Carriers Considering Risk-Reducing Mastectomy. (PubMed, Curr Oncol)
    Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future.
    Review • Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)