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    BIOMARKER:

    PALB2 mutation

    i
    Entrez ID:
    79728
    Related biomarkers:
    CNA
    Others
    Related tests:
    5d
    ORCHID: Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (clinicaltrials.gov)
    P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
    |
    ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
    |
    Lynparza (olaparib)
    7d
    Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov)
    P2, N=88, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Mar 2026
    Trial completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA (Breast cancer early onset)
    |
    PALB2 mutation • BRCA mutation
    |
    cisplatin • gemcitabine • veliparib (ABT-888)
    10d
    Breast Cancer: A Heterogeneous Pathology. Prognostic and Predictive Factors - A Narrative Review. (PubMed, Chirurgia (Bucur))
    Moreover, the implementation of Molecular Tumor Boards further enhances personalized treatment strategies, contributing to improved patient outcomes and survival rates. This review underscores the significance of tailored therapeutic approaches and highlights the dynamic evolution of breast cancer in clinical practice.
    Review • Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • PALB2 (Partner and localizer of BRCA2)
    |
    TP53 mutation • PIK3CA mutation • PTEN mutation • PALB2 mutation
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MammaPrint • EndoPredict® • Oncotype DX Breast Recurrence Score®Test
    14d
    Response to PARP inhibitor in EGFR-tyrosine kinase inhibitor-resistant metastatic lung adenocarcinoma with germline PALB2 mutation. (PubMed, Anticancer Drugs)
    We present a case of EGFR-tyrosine kinase inhibitor-resistant metastatic lung adenocarcinoma with a germline PALB2 mutation that was treated with fluzoparib (an orally administered PARPi). The treatment achieved surprising results and lasted for more than 4.5 months. Our study provided evidence that metastatic lung adenocarcinoma with germline PALB2 could benefit from PARPi, which improves patient outcomes.
    Journal • PARP Biomarker
    |
    EGFR (Epidermal growth factor receptor) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
    |
    HRD • PALB2 mutation
    |
    AiRuiYi (fluzoparib)
    21d
    Neoadjuvant chemotherapy response and genetic susceptibility in recently parous women with breast cancer. (PubMed, medRxiv)
    Post-partum BC occurrence is not increased in BRCA1/2 carriers; effects of rarer susceptibility genes may differ. These important effects of parity on BC in young women and those at genetic risk warrant larger prospective studies.
    Journal • BRCA Biomarker • IO biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    PALB2 mutation
    1m
    Mutations in homologous recombination repair genes in patients with metastatic endometrial cancer: association with clinical characteristics and prognosis. (PubMed, J Gynecol Oncol)
    Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns. However, the prognoses are similar regardless of HRR status.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • 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) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    TP53 mutation • MSI-H/dMMR • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    1m
    Stand Up to Cancer: MAGENTA (Making Genetic Testing Accessible) (clinicaltrials.gov)
    P=N/A, N=5200, Suspended, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2026 | Recruiting --> Suspended | Trial primary completion date: Apr 2024 --> Apr 2026
    Trial completion date • Trial suspension • Trial primary completion date
    |
    ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)
    |
    PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    1m
    Beyond failure of endocrine-based therapies in HR+/HER2 negative advanced breast cancer: what before chemotherapy? A glimpse into the future. (PubMed, Crit Rev Oncol Hematol)
    Trastuzumab-deruxtecan has been proven meaningfully superior to chemotherapy either in 1st and later lines after progression to CDK4/6i in HER2-low ABC and results with other ADCs as Sacituzumab Govitecan and Datopotamab-deruxtecan are promising, but the definition of cross-resistance between these drugs sharing either antibody or payload is crucial before implementing them in a useful sequence. On the other hand, the results obtained with immune checkpoint inhibitors (ICIs) in HR+/HER2-ABC contrarily to the early setting are disappointing up to now, but investigations of ICIs in combination with other targeted drugs which may increase immune response and the search for better markers of activity are under way. Moreover the anticipation in upfront treatment of ADCs or PARPi in patients with features of putative endocrine resistance and/or of less sensitiviy to CDK4/6i and the choice of therapy in patients recurring during or soon after adjuvant CDK4/6i and olaparib represent further challenges for the future.
    Review • Journal • BRCA Biomarker • PARP Biomarker • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • PALB2 (Partner and localizer of BRCA2)
    |
    HER-2 positive • HR positive • HER-2 negative • PALB2 mutation • HR positive + HER-2 negative • HER-2 negative + HR positive + BRCA mutation
    |
    Lynparza (olaparib) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Trodelvy (sacituzumab govitecan-hziy) • Datroway (datopotamab deruxtecan)
    2ms
    HRPCa-II: Evaluation of a Multimodal Strategy for Early Diagnosis of Men At High Genetic Risk of Prostate Cancer (clinicaltrials.gov)
    P=N/A, N=880, Not yet recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Dec 2029 --> Mar 2030 | Trial primary completion date: Dec 2029 --> Mar 2030
    Trial completion date • Trial primary completion date
    |
    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) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • HOXB13 (Homeobox B13)
    |
    PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • BARD1 mutation
    2ms
    Association between DNA damage repair alterations and outcomes to 177Lu-PSMA-617 in advanced prostate cancer. (PubMed, ESMO Open)
    DDR alterations were not associated with outcomes following LuPSMA. This has implications for treatment sequencing in mCRPC, particularly in patients with DDR alterations.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • RAD51 (RAD51 Homolog A)
    |
    ATM mutation • PALB2 mutation • CDK12 mutation
    |
    Pluvicto (lutetium Lu 177 vipivotide tetraxetan)
    2ms
    Informatics strategies for early detection and risk mitigation in pancreatic cancer patients. (PubMed, Neoplasia)
    Additionally, this review points to future directions in PC diagnostics, including next-generation imaging, molecular biomarkers, and personalized medicine, aiming to overcome current diagnostic challenges and improve survival rates. Ultimately, the review advocates the adoption of informatics and AI-driven strategies to enhance early detection, reduce morbidity, and save lives in the fight against pancreatic cancer.
    Review • Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    PALB2 mutation
    |
    CancerSEEK
    2ms
    Comprehensive Genetic Profile of Chinese Muscle-Invasive Bladder Cancer Cohort. (PubMed, Clin Genitourin Cancer)
    Our study provided comprehensive insights into genomic alterations in a cohort of Chinese MIBC, which could provide potential clues for clinical applications.
    Journal • Tumor mutational burden
    |
    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR3 (Fibroblast growth factor receptor 3) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ERCC2 (Excision repair cross-complementation group 2) • KMT2C (Lysine Methyltransferase 2C) • MUC16 (Mucin 16, Cell Surface Associated) • TTN (Titin) • AHNAK2 (AHNAK Nucleoprotein 2) • MUC4 (Mucin 4, Cell Surface Associated) • CDC27 (Cell Division Cycle 27)
    |
    TP53 mutation • TMB-H • PALB2 mutation
    2ms
    Los olvidados: Non-BRCA variants associated with Hereditary breast cancer in Mexican population. (PubMed, Breast Cancer Res)
    Multi-gene testing implementation improves the detection of often overlooked genes related to HBOC pathogenesis and treatment. Non-BRCA GPVs in Northern Mexico correspond to one-third of the HBOC cases, including HR and DDR pathways genes that would be misdiagnosed if not tested. HR patient carriers are potential targets of iPARP therapies. The optimal approach to cancer treatment for non-BRCA mutation carriers warrants further investigation to develop newer therapies.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • MUTYH (MutY homolog)
    |
    PALB2 mutation
    2ms
    Sialoblastomas With Solid Pattern Have FGFR2 Mutations and an Unfavorable Prognosis. (PubMed, Am J Surg Pathol)
    Overall, SBLs can be stratified into solid and non-solid patterns, with solid pattern tumors usually having FGFR2 mutations, increasing the risk of recurrence and metastasis. This stratification underscores the importance of genetic and morphologic profiling for predicting the prognosis of SBLs.
    Journal
    |
    FGFR2 (Fibroblast growth factor receptor 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • PALB2 (Partner and localizer of BRCA2)
    |
    FGFR2 mutation • PALB2 mutation • HRAS mutation
    2ms
    A Study of Olaparib and Pembrolizumab in People with Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer (clinicaltrials.gov)
    P2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • HR positive + HER-2 negative • RAD51 mutation • HER-2 negative + HR positive + BRCA mutation
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib)
    2ms
    Preliminary Evaluation of Screening for Pancreatic Cancer in Patients with Inherited Genetic Risk (clinicaltrials.gov)
    P=N/A, N=200, Recruiting, Abramson Cancer Center at Penn Medicine | Trial completion date: May 2028 --> May 2030 | Trial primary completion date: May 2026 --> May 2028
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation
    3ms
    Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)
    P1/2, N=71, Recruiting, Yonsei University | Not yet recruiting --> Recruiting | Trial completion date: May 2023 --> May 2025 | Trial primary completion date: Dec 2022 --> Dec 2024
    Enrollment open • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
    |
    HER-2 positive • BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • CHEK1 expression
    |
    Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
    3ms
    CERTIS1: Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies (clinicaltrials.gov)
    P1/2, N=490, Recruiting, AstraZeneca | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Jan 2026 --> Aug 2026
    Trial completion date • Trial primary completion date
    |
    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) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 negative • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation
    |
    temozolomide • Enhertu (fam-trastuzumab deruxtecan-nxki) • Datroway (datopotamab deruxtecan) • AZD9574
    3ms
    High- and Moderate-Risk Variants Among Breast Cancer Patients and Healthy Donors Enrolled in Multigene Panel Testing in a Population of Central Russia. (PubMed, Int J Mol Sci)
    The BLM, NBN, and MUTYH genes did not demonstrate associations with BC risk. Finding deleterious mutations in BC patients is important for diagnosis and management; in controls, it opens up the possibility of prevention and early diagnostics.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • MUTYH (MutY homolog) • XRCC2 (X-Ray Repair Cross Complementing 2)
    |
    PALB2 mutation • RAD51C mutation • RAD50 mutation • BARD1 mutation • BLM mutation • NBN mutation
    3ms
    NCI 9938: M6620 and Irinotecan Hydrochloride in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery (clinicaltrials.gov)
    P1, N=66, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2025
    Trial completion date • Combination therapy • Surgery • Metastases
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation
    |
    irinotecan • berzosertib (M6620)
    3ms
    Proline variants in the BRCA1 coiled-coil domain disrupt folding and binding to PALB2. (PubMed, Protein Sci)
    Structural analysis indicates that all BRCA1 mutations to proline tested disrupt α-helix formation and therefore are not well tolerated even when located at positions outside of the PALB2-binding interface. This assay and the structural hypothesis described will be helpful for assessing risk for variants identified in the future in the BRCA1/PALB2 interaction domains.
    Journal • BRCA Biomarker
    |
    BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2)
    |
    BRCA1 mutation • PALB2 mutation
    3ms
    Four pathogenic variants co-occurring in a MINAS early-onset breast cancer. (PubMed, Tumori)
    Currently, there are no predictive tools available to determine organ-specific cancer risk in MINAS patients. Given the uncertainty in predicting the phenotypic effect of multiple variants in CSGs, ongoing clinical surveillance and sharing data from complex cases are crucial for improving risk stratification in this condition.
    Journal
    |
    PALB2 (Partner and localizer of BRCA2) • PMS2 (PMS1 protein homolog 2) • MUTYH (MutY homolog)
    |
    PALB2 mutation
    3ms
    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)
    3ms
    Response to Carboplatin and Paclitaxel in the treatment of hereditary breast ovarian cancer syndrome (HBOC): a case report. (PubMed, J Pak Med Assoc)
    This dynamic treatment not only led to nearly complete remission of high-grade ovarian serous cancer but also triggered regression in grade-2 invasive ductal breast cancer after just a few rounds of chemotherapy. Consequently, what started as palliative care evolved into a curative triumph.
    Journal • BRCA Biomarker
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PALB2 (Partner and localizer of BRCA2) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1)
    |
    TP53 mutation • BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CHEK1 mutation • CHEK1 expression
    |
    carboplatin • paclitaxel
    3ms
    Severe Radiation-Induced Brachial Plexopathy: A Case Report on Radiation Toxicity in a Patient With Invasive Ductal Carcinoma. (PubMed, Cureus)
    Here, we present a case of a 50-year-old woman with stage IIIA invasive ductal carcinoma of the left breast who had genetic testing revealing pathogenic ATM mutations (c.5290del and c.4396C>G) and a PALB2 mutation (c.1619dup). While guidelines suggest that adjuvant radiation therapy is safe for patients with ATM mutations, this patient experienced severe radiation-induced toxicities, including brachial plexopathy. These ATM mutations have not previously been described as imparting severe radiation-associated toxicities.
    Journal
    |
    ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2)
    |
    PALB2 mutation
    4ms
    Elucidating acquired PARP inhibitor resistance in advanced prostate cancer. (PubMed, Cancer Cell)
    For BRCA2 HomDels, selection for rare subclones without BRCA2-HomDel is observed following PARPi, confirmed by single circulating-tumor-cell genomics, biopsy fluorescence in situ hybridization (FISH), and RNAish. These data support the need for restored HRR function in PARPi resistance.
    Journal • BRCA Biomarker • PARP Biomarker • Metastases
    |
    BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
    |
    PALB2 mutation • BRCA mutation
    4ms
    Survival Outcomes and Genetic Characteristics of Resected Pancreatic Acinar Cell Carcinoma. (PubMed, Ann Surg Oncol)
    Resection of pACC is associated with favorable survival outcomes, even in the setting of oligometastatic disease. Mutations in the HRR pathway are common, providing opportunities for potential targeted therapeutic options.
    Journal • Tumor mutational burden • BRCA Biomarker
    |
    TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
    |
    TMB-H • PALB2 mutation
    |
    5-fluorouracil • oxaliplatin • irinotecan • leucovorin calcium
    4ms
    CASE6119: Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Triple-Negative Breast Cancer (clinicaltrials.gov)
    P1, N=45, Recruiting, George T. Budd | Trial completion date: Mar 2025 --> Nov 2025 | Trial primary completion date: Nov 2024 --> May 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • PRL (Prolactin)
    |
    BRCA1 mutation • HER-2 negative • PALB2 mutation • ER negative • PGR negative
    |
    alpha-lactalbumin vaccine
    4ms
    Exactis-03: Combination of Olaparib and Navitoclax in Women with HGSC and TNBC (clinicaltrials.gov)
    P1, N=36, Active, not recruiting, Sunnybrook Health Sciences Centre | Recruiting --> Active, not recruiting | Trial primary completion date: Apr 2024 --> Mar 2025
    Enrollment closed • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
    |
    BRCA2 mutation • BRCA1 mutation • PALB2 mutation
    |
    Lynparza (olaparib) • navitoclax (ABT 263)
    4ms
    Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer with Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)
    P1; Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Nov 2024 | Trial primary completion date: Dec 2025 --> Nov 2024
    Trial completion date • Trial primary completion date • Trial completion
    |
    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
    4ms
    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
    4ms
    Radiation Therapy (RT) and Chemotherapy for the Treatment of Pancreatic Cancer With Homologous Recombination Deficiency That Has Spread to the Liver (clinicaltrials.gov)
    P1; Trial completion date: Dec 2024 --> Dec 2025 | 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) • 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
    5ms
    Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study (SABCS 2024)
    This study reported a cohort of Taiwanese breast cancers harboring mutations in BRCA1, BRCA2, and PALB2 through tumor-only sequencing, which underscores the impact of these genes on breast cancer risk and potential therapeutic opportunities. Tumor-only sequencing has enabled a greater number of patients to uncover their genomic alterations, offering additional insights for management strategies. These include recommendations for germline testing and the prospective utilization of PARP inhibitors to augment treatment efficacy.
    PARP Biomarker • BRCA 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) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • RAD51 (RAD51 Homolog A)
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    BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRCA mutation • RAD51 mutation
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    Oncomine™ Comprehensive Assay v3M
    5ms
    Serial circulating tumor DNA (ctDNA) assessment to predict treatment response and identify genomic evolution in patients with metastatic breast cancer (mBC). (SABCS 2024)
    Decrease in TF, but not maxVAF, at 1-2 weeks after starting next therapy is correlated with clinical response at time of restaging and can provide an early assessment of treatment response. Genomic evolution with both emerging and disappearing alterations, including in genes clinically actionable in breast cancer as well as genes likely associated with CH, was frequently identified by serial liquid biopsies, both at time of progression and while on treatment.
    Clinical • BRCA Biomarker • Circulating tumor DNA • Metastases
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • DNMT3A (DNA methyltransferase 1) • PALB2 (Partner and localizer of BRCA2)
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    TP53 mutation • PIK3CA mutation • ATM mutation • PTEN mutation • PALB2 mutation
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    FoundationOne® Liquid CDx
    5ms
    Genomic and transcriptomic analyses of residual invasive triple-neg breast cancer after neoadjuvant chemotherapy in prospective MIRINAE trial (a randomized phase II trial of adjuvant atezolizumab + capecitabine versus capecitabine; KCSG-BR18-21). (SABCS 2024)
    TIL-high tumors were associated with immune-enriched cancer including BLIA and TME subtypes. Ongoing analysis of invasive disease-free survival as the primary endpoint in each arm of MIRINAE trial and the role of atezolizumab in association with genomic features will provide deeper insights into the role of ICIs as adjuvant therapy.
    P2 data • Clinical • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • PALB2 (Partner and localizer of BRCA2) • IFNG (Interferon, gamma) • LAG3 (Lymphocyte Activating 3) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CXCL9 (Chemokine (C-X-C motif) ligand 9) • CD4 (CD4 Molecule) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • IRF4 (Interferon regulatory factor 4) • CD3D (CD3d Molecule) • GZMK (Granzyme K) • NDRG1 (N-Myc Downstream Regulated 1)
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    TP53 mutation • BRCA1 mutation • PIK3CA mutation • PALB2 mutation • PIK3R1 mutation
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    FoundationOne® CDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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    Tecentriq (atezolizumab) • capecitabine
    5ms
    Clinical Outcomes and the 21-Gene Recurrence Score Assay in Early-Stage Breast Cancer Associated with CHEK2, ATM and PALB2 Germline Pathogenic Variants (SABCS 2024)
    Our data demonstrate that higher Oncotype RS, CHEK2 mutations, lymphatic and vascular invasion, and higher Ki67 levels were identified as predictors of poorer RFS. Conversely, older age (>50 years), adjuvant ET, and adjuvant XRT were associated with improved RFS. Importantly, the presence of ATM, CHEK2, or PALB2 mutations did not significantly impact OS.
    Clinical data • Clinical
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2)
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    ER positive • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CHEK2 mutation • HR positive + HER-2 negative • PGR negative • HER-2 negative + ER positive
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    Oncotype DX Breast Recurrence Score®Test
    5ms
    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
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    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)
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    BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation • AKT1 mutation • HRD signature • BRCA1 fusion
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    FoundationOne® CDx
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    Keytruda (pembrolizumab)
    5ms
    PARP Inhibitors in Pancreatic Cancer with Homologous Recombination Repair Gene Mutations: A Single-Institution Experience. (PubMed, Cancers (Basel))
    PARP inhibitors may be considered for patients with advanced pancreatic cancer harboring pathogenic alterations of BRCA who cannot tolerate standard chemotherapy. Maintenance PARPis can be considered in selected patients with non-BRCA/non-PALB2 HRR mutations.
    Journal • BRCA Biomarker • PARP Biomarker
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    HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)
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    PALB2 mutation • PARP1 mutation
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    Lynparza (olaparib)
    5ms
    Niraparib in Patients With Pancreatic Cancer (clinicaltrials.gov)
    P2, N=32, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2025 --> Feb 2026 | Trial primary completion date: Sep 2024 --> Sep 2025
    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) • CHEK2 (Checkpoint kinase 2)
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    BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation
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    Zejula (niraparib)
    5ms
    Cohort Study of Pancreatic Cancer Risk (clinicaltrials.gov)
    P=N/A, N=419, Active, not recruiting, Mayo Clinic | N=2000 --> 419
    Enrollment change
    |
    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • APC (APC Regulator Of WNT Signaling Pathway) • EPCAM (Epithelial cell adhesion molecule)
    |
    TP53 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • APC mutation • MSH2 mutation • PMS2 mutation
    5ms
    The Cancer of the Pancreas Screening-5 CAPS5)Study (clinicaltrials.gov)
    P3, N=9000, Recruiting, Johns Hopkins University | Trial primary completion date: Oct 2024 --> Oct 2025
    Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH2 (MutS Homolog 2) • PRSS1 (Serine Protease 1) • CA 19-9 (Cancer antigen 19-9) • CTRC (Chymotrypsin C)
    |
    BRCA1 mutation • PALB2 mutation
    5ms
    Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series. (PubMed, Cancers (Basel))
    One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months...One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.
    Journal • BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD74 (CD74 Molecule) • PALB2 (Partner and localizer of BRCA2) • CEACAM5 (CEA Cell Adhesion Molecule 5) • CDH6 (Cadherin 6) • MMP1 (Matrix metallopeptidase 1)
    |
    BRCA2 mutation • BRCA1 mutation • NTRK1 fusion • RET fusion • ATM mutation • PALB2 mutation • KRAS wild-type
    |
    Retevmo (selpercatinib)