News - PALB2 mutation

23h

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.

23 hours ago

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

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

3 days ago

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)

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.

4 days ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • PALB2 (Partner and localizer of BRCA2)

BRCA1 mutation • PALB2 mutation

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.

6 days ago

Journal

PALB2 (Partner and localizer of BRCA2) • PMS2 (PMS1 protein homolog 2) • MUTYH (MutY homolog)

PALB2 mutation

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

6 days ago

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)

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.

7 days ago

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

12d

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.

12 days ago

Journal

ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2)

PALB2 mutation

25d

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.

25 days ago

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

26d

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.

26 days ago

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

29d

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

29 days ago

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

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

1 month ago

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)

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

1 month ago

Trial completion • Trial completion date • Trial primary completion date

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

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

1 month ago

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

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, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

1 month ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 mutation • PALB2 mutation

MSK-IMPACT

cisplatin • gemcitabine

2ms

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.

2 months ago

BRCA Biomarker • PARP Biomarker

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)

BRCA2 mutation • BRCA1 mutation • PALB2 mutation • BRCA mutation • RAD51 mutation

Oncomine™ Comprehensive Assay v3M

2ms

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.

2 months ago

Clinical • BRCA Biomarker • Circulating tumor DNA • Metastases

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)

TP53 mutation • PIK3CA mutation • ATM mutation • PTEN mutation • PALB2 mutation

FoundationOne® Liquid CDx

2ms

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.

2 months ago

Clinical • P2 data • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

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)

TP53 mutation • BRCA1 mutation • PIK3CA mutation • PALB2 mutation • PIK3R1 mutation

FoundationOne® CDx • Prosigna™ Breast Cancer Prognostic Gene Signature Assay

Tecentriq (atezolizumab) • capecitabine

2ms

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.

2 months ago

Checkpoint inhibition • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)

BRCA2 mutation • BRCA1 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation • AKT1 mutation • HRD signature • BRCA1 fusion

FoundationOne® CDx

Keytruda (pembrolizumab)

2ms

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.

2 months ago

Clinical • Clinical data

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)

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

Oncotype DX Breast Recurrence Score®Test

2ms

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.

2 months ago

Journal • BRCA Biomarker • PARP Biomarker

HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset)

PALB2 mutation • PARP1 mutation

Lynparza (olaparib)

2ms

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

2 months ago

Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation

Zejula (niraparib)

2ms

Cohort Study of Pancreatic Cancer Risk (clinicaltrials.gov)

P=N/A, N=419, Active, not recruiting, Mayo Clinic | N=2000 --> 419

2 months ago

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

2ms

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

2 months ago

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

2ms

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.

2 months ago

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)

2ms

TBCRC 048: Olaparib in Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=114, Active, not recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

2 months ago

Trial completion date • Trial primary completion date • Metastases

PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset) • 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) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

BRCA2 mutation • BRCA1 mutation • HR positive • PALB2 mutation • PGR positive • BRCA mutation

Lynparza (olaparib)

2ms

Understanding genetic variations associated with familial breast cancer. (PubMed, World J Surg Oncol)

Familial breast cancer has been linked to several genetic diseases and mutations, according to studies. Screening for genetic disorders is recommended by National Comprehensive Cancer Network recommendations. Evaluation of breast cancer candidate variations and risk loci may improve individual risk assessment. Only high- and moderate-risk gene variations have clinical guidelines, whereas low-risk gene variants require additional investigation. With increasing use of NGS technology, more linkage with rare genes is being discovered.

2 months ago

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) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1)

ATM mutation • PALB2 mutation • CHEK2 mutation • BRIP1 mutation

3ms

D5330C00004: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents (clinicaltrials.gov)

P1/2, N=466, Recruiting, AstraZeneca | Trial completion date: Jul 2026 --> Mar 2025 | Trial primary completion date: Jul 2026 --> Mar 2025

3 months ago

Trial completion date • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

HER-2 negative • HRD • PALB2 mutation • RAD51C mutation • BRCA mutation • RAD51 mutation

Lynparza (olaparib) • carboplatin • Imfinzi (durvalumab) • ceralasertib (AZD6738) • saruparib (AZD5305)

3ms

PAVO: Niraparib in the Treatment of Patients with Advanced PALB2 Mutated Tumors (clinicaltrials.gov)

P2, N=22, Terminated, Tempus AI | Active, not recruiting --> Terminated; Recruitment challenges

3 months ago

Trial termination

PALB2 mutation

Zejula (niraparib)

3ms

CHANGEABLE: Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=37, Completed, Fudan University | Recruiting --> Completed

3 months ago

Trial completion • Metastases

HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • 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) • WRN (WRN RecQ Like Helicase) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • ATM mutation • PALB2 mutation • CDK12 mutation • BAP1 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • HR positive + HER-2 negative • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • PTEN mutation + HR positive • CHEK1 expression • HER-2 negative + HR positive + BRCA mutation

Herceptin (trastuzumab) • Zejula (niraparib) • Puyouheng (pucotenlimab)

3ms

NBG-19-01: NordicTrip, a Translational Study of Preoperative Chemotherapy in TNBC (clinicaltrials.gov)

P3, N=325, Recruiting, Lund University Hospital | N=920 --> 325 | Trial primary completion date: Jun 2023 --> Jul 2025

3 months ago

Enrollment change • Trial primary completion date

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

PD-L1 expression • BRCA1 mutation • PALB2 mutation • ER negative

Keytruda (pembrolizumab) • carboplatin • paclitaxel • capecitabine • cyclophosphamide • epirubicin

3ms

Talazoparib Monotherapy in PALB2 Mutation Associated Advanced Breast Cancer (clinicaltrials.gov)

P2, N=30, Recruiting, Stanford University | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

3 months ago

Trial completion date • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2)

HER-2 negative • PALB2 mutation

Talzenna (talazoparib)

3ms

Mutation Spectrum Comparison between Benign Breast Lesion Cohort, Unselected Cancer Cohort and High-Risk Breast Cancer Cohort. (PubMed, Cancers (Basel))

An unexpectedly high mutation rate of total 2% was found in the NC cohort but it was only 0.3% and 0.5% in the HR cohort and CC cohort, respectively. Our results show a clinical need to enhance genetic testing of unselected breast cancer patients to identify the high-risk patients.

3 months ago

Journal • BRCA Biomarker

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) • CDH1 (Cadherin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

TP53 mutation • PTEN mutation • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation

3ms

Clinical Impact of Constitutional Genomic Testing on Current Breast Cancer Care. (PubMed, Clin Oncol (R Coll Radiol))

However, the lack of long-term clinical outcome data and incomplete understanding of variants, particularly for moderate-risk genes limits clinical application. In this review, we have summarized the key functions, risks, and prognosis of breast-cancer-predisposing genes listed in the National Health Service (NHS) England National Genomic Test Directory for inherited breast cancer and provide an update on current management implications including surgery, radiotherapy, systemic treatments, and post-treatment surveillance.

3 months ago

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) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

TP53 mutation • BRCA1 mutation • PALB2 mutation • RAD51C mutation • RAD51D mutation • RAD51 mutation

3ms

Circulating Tumor DNA (ctDNA) Monitoring in the Assessment and Prediction of the Efficacy of PARP Inhibitors (PARPi) (clinicaltrials.gov)

P=N/A, N=30, Recruiting, Sun Yat-sen University | Trial completion date: Aug 2023 --> Aug 2025

3 months ago

Trial completion date • Circulating tumor DNA

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • 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)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation • BRCA1 mutation + ATM mutation • CHEK1 expression

7ms

Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Triple-Negative Breast Cancer (clinicaltrials.gov)

P1, N=45, Recruiting, George T. Budd | Trial completion date: Sep 2024 --> Mar 2025 | Trial primary completion date: May 2024 --> Nov 2024

7 months ago

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

8ms

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO (clinicaltrials.gov)

P2, N=11, Active, not recruiting, Institut fuer Frauengesundheit | Recruiting --> Active, not recruiting | N=89 --> 11 | Trial primary completion date: Jan 2024 --> Jan 2025

8 months ago

Enrollment closed • Enrollment change • Trial primary completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • XRCC2 (X-Ray Repair Cross Complementing 2) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

BRCA2 mutation • BRCA1 mutation • HER-2 amplification • HER-2 negative • HRD • ATM mutation • PALB2 mutation • ER positive + PGR positive • CHEK2 mutation • PGR positive • RAD51C mutation • RAD51D mutation • BARD1 mutation • RAD51 mutation

Keytruda (pembrolizumab) • Lynparza (olaparib)

8ms

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.

8 months ago

Clinical • IO biomarker

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

Oncomine™ Comprehensive Assay v3M • Oncomine™ TCR Beta-LR Assay

8ms

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.

8 months ago

Retrospective data • Journal

PALB2 (Partner and localizer of BRCA2)

PALB2 mutation

8ms

KNIGHTS: High-Risk Metachronous Oligometastatic Prostate Cancer Trial (clinicaltrials.gov)

P2, N=88, Recruiting, University of Maryland, Baltimore | Not yet recruiting --> Recruiting

8 months ago

Enrollment open • Metastases

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • RAD54L (DNA Repair And Recombination Protein RAD54)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • FANCA mutation

Zejula (niraparib) • abiraterone acetate • prednisone

8ms

Studying the Safety and Determining the Optimal Dose of Novobiocin in Patients With Tumors That Have Alterations in DNA Repair Genes (clinicaltrials.gov)

P1, N=30, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

8 months ago

Enrollment open

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDK12 (Cyclin dependent kinase 12) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • 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)) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCC (FA Complementation Group C)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • RAD51B mutation • BARD1 mutation • BLM mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation • RAD51 mutation

8ms

Cabozantinib and Pamiparib for the Treatment of Advanced of Refractory Solid Tumors (clinicaltrials.gov)

P1, N=44, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

8 months ago

Enrollment open • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • CHEK2 (Checkpoint kinase 2) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • CHEK1 (Checkpoint kinase 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting)

BRCA2 mutation • BRCA1 mutation • ATM mutation • PALB2 mutation • CHEK2 mutation • RAD50 mutation • CHEK1 mutation • CHEK1 expression

Cabometyx (cabozantinib tablet) • Partruvix (pamiparib)

8ms

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.

8 months ago

Journal • BRCA Biomarker

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