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GENE:

RAD51D (RAD51 paralog D)

News alerts, weekly reports and conference planners

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

Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations (clinicaltrials.gov)

P2, N=36, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2026

9 days ago

Trial completion date • Trial primary completion date • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • 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) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • BACH1 (BTB Domain And CNC Homolog 1) • 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)

BRCA2 mutation • BRCA1 mutation • ATM mutation

Talzenna (talazoparib)

Investigating the effects of the ARG258HIS mutation on RAD51C in inherited Fanconi Anemia and cancer disease. (PubMed, J Biomol Struct Dyn)

These simulations highlighted alterations in conformational dynamics, the Free Energy Landscape (FEL), and intrinsic molecular motions induced by the mutation, suggesting structural destabilization that could disrupt its function. This observed destabilization in RAD51C due to mutations offers valuable insights that may serve as diagnostic markers for individuals carrying these mutations, particularly in Fanconi anemia.

9 days ago

Journal

RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

RAD51C mutation • RAD51 mutation

12d

A phase II study evaluating safety and efficacy of niraparib in patients with previously treated homologous recombination defective metastatic esophageal/gastroesophageal junction/proximal gastric adenocarcinoma. (PubMed, Front Oncol)

The most common adverse events seen were anemia, fatigue, and thrombocytopenia. In patients with metastatic EAC, single agent niraparib as second line therapy is not an effective option.

12 days ago

P2 data • Journal • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • PARP2 (Poly(ADP-Ribose) Polymerase 2)

FANCA deletion

Zejula (niraparib)

27d

Association between homologous recombination deficiency and time to treatment failure to platinum-based chemotherapy for pancreatic cancer by using the C-CAT database. (PubMed, J Gastroenterol)

Our findings suggest that HRR-related genetic abnormalities might be predictive of TTF in platinum-based chemotherapy for PC.

27 days ago

Journal • BRCA Biomarker

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)

HRD • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • BARD1 mutation

FoundationOne® CDx • OncoGuide™ NCC Oncopanel System

gemcitabine • 5-fluorouracil • albumin-bound paclitaxel • irinotecan • leucovorin calcium

Mismatch Repair (MMR) and Homologous Recombination (HR) Deficiency: Real-Life Applications of biomarkers for complementary approaches in Epithelial Ovarian Cancer (AIOM 2024)

HRD genomic instability tests and multigene panel assessments serve as synergistic tools in EOC clinical settings, proving essential for identifying patients likely to benefit from PARPi therapy. These tools also enhance the detection of HRR and MMR gene variants, aiding in preventive care. Further investigations into the genetic profiles of HRD-negative tumors are crucial for advancing cancer risk management and developing novel therapeutic avenues.

1 month ago

Clinical • Mismatch repair • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • MUTYH (MutY homolog)

BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type

Myriad myChoice® CDx

Pathogenic variants in cancer susceptibility genes predispose to Ductal Carcinoma In situ of the breast. (PubMed, Clin Cancer Res)

The enrichment of PVs in ATM, BRCA1, BRCA2, CHEK2 and PALB2 among women with DCIS suggests that multigene panel testing may be appropriate for women with DCIS. Elevated risks of contralateral breast cancer in carriers of PVs in high penetrance genes with DCIS confirmed the utility of testing for surgical decision-making.

1 month ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

Oncologic outcomes of incidental serous tubal intraepithelial carcinoma and associated high-grade serous carcinoma in high-risk patients undergoing risk-reducing surgery. (PubMed, Int J Gynecol Cancer)

The study supports the critical need for timely risk-reducing surgery in high-risk populations, as well as a comprehensive pathologic examination along with vigilant post-operative surveillance. Consensus guidelines for management of serous tubal intraepithelial carcinoma are necessary to identify a group of patients at higher risk of progression to primary peritoneal carcinoma and optimize patient care.

1 month ago

Journal • Surgery

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)

2ms

Germline genetic variants in a case of familial cancer: RAD51D and four other co-segregated variants. (PubMed, J Genet)

All the four family members show segregation of RAD51D (rs200564819). Other incidental findings ADAMTS13 (rs142572218) and SYCE1 (rs201873178) genetic variants in proband and son, and LIAS (rs546751789) and PDHA1(rs747051654) genetic variants in son have also been reported.

2 months ago

Journal

RAD51D (RAD51 paralog D) • LIAS (Lipoic Acid Synthetase) • PDHA1 (Pyruvate Dehydrogenase E1 Subunit Alpha 1)

2ms

Germline variants of homology-directed repair or mismatch repair genes in cervical cancer. (PubMed, Int J Cancer)

Taken together, our study supports a potentially risk-modifying role of MMR and HDR germline variants in cervical cancer but no association with HPV-negative status. These variants may be exploitable in future therapeutic managements.

2 months ago

Journal • Mismatch repair • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSH6 (MutS homolog 6) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCM (FA Complementation Group M) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)

2ms

RAD51 Paralogs and RAD51 Paralog Complexes BCDX2 and CX3 Interact with BRCA2. (PubMed, bioRxiv)

Furthermore, the interaction with RAD51B is dependent upon an FxxA motif located on a surface exposed region of the CTD. Our study has identified novel interactions between the RAD51 paralogs and BRCA2 and further demonstrated that a previously unrecognized FxxA motif located within a mobile element of RAD51B is critical for the interaction.

2 months ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA2 (Breast cancer 2, early onset) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • XRCC2 (X-Ray Repair Cross Complementing 2) • XRCC3 (X-Ray Repair Cross Complementing 3)

RAD51C mutation • RAD51D mutation • RAD51B mutation • RAD51 mutation

2ms

TRIUMPH: Trial of Rucaparib in Patients With Metastatic Hormone-Sensitive Prostate Cancer Harboring Germline DNA Repair Gene Mutations (clinicaltrials.gov)

P2, N=12, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | N=30 --> 12

2 months ago

Trial completion • Enrollment change • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • 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)

CHEK2 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • RAD50 mutation • FANCF mutation • NBN mutation • FANCG mutation • FANCI mutation • FANCM mutation

Rubraca (rucaparib)

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

Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer. (PubMed, Cancer Sci)

Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.

2 months ago

Journal • BRCA Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

Avastin (bevacizumab)

2ms

PROGRESS: Prostate Cancer Genetic Risk Evaluation and Screening Study (clinicaltrials.gov)

P=N/A, N=400, Recruiting, Massachusetts General Hospital | N=200 --> 400

2 months ago

Enrollment change

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • GEN1 (GEN1 Holliday junction 5' flap endonuclease) • HOXB13 (Homeobox B13)

CHEK2 mutation • BRIP1 mutation • RAD51C mutation • FANCA mutation • RAD51D mutation • PMS2 mutation • NBN 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

Homologous recombination deficiency gene panel analysis results in synchronous endometrial and ovarian cancers. (PubMed, Rev Assoc Med Bras (1992))

Pathogenic variations confirming the diagnosis of synchronous endometrial ovarian cancer with genetic alterations were identified in all but one case. ATM gene mutation emerged as the most common alteration and has a potential association with a favorable prognosis.

3 months ago

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) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54)

TP53 mutation • HRD • RAD51D mutation • BARD1 mutation • RAD54L mutation • TP53 mutation + ATM mutation

3ms

The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer. (PubMed, Ann Surg Oncol)

Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.

3 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • NF1 (Neurofibromin 1) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

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

What About the Others? Clinical Management of Gynecologic Cancer Risk in Patients With Moderate-Risk Hereditary Cancer Genes (ATM, BRIP1, RAD51C, RAD51D, and PALB2). (PubMed, Clin Obstet Gynecol)

The associated cancer risks with moderate-penetrance genes are rapidly evolving and present variable risks for the provider counseling the patient. In this review, we detail the cancer risk and management of patients with germline PV in the moderate-risk hereditary cancer genes ATM, BRIP1, RAD51C, RAD51D, and PALB2.

3 months ago

Journal

ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

3ms

Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer (clinicaltrials.gov)

P2, N=80, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial primary completion date: Sep 2026 --> Aug 2027

3 months ago

Enrollment open • Trial primary completion date

TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CDH1 (Cadherin 1) • 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) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • AGR2 (Anterior gradient 2)

TP53 mutation • ATM mutation • PTEN mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • PMS2 mutation • BARD1 mutation • NBN mutation

tamoxifen • acolbifene

3ms

Validation of the BOADICEA model for epithelial tubo-ovarian cancer risk prediction in UK Biobank. (PubMed, Br J Cancer)

BOADICEA, implemented in CanRisk ( www.canrisk.org ), provides valid 10-year EOC risks and can facilitate clinical decision-making in EOC risk management.

3 months ago

Journal

3ms

BRACeD: Carboplatin or Olaparib for BRcA Deficient Prostate Cancer (clinicaltrials.gov)

P2, N=100, Recruiting, VA Office of Research and Development | Trial primary completion date: Aug 2024 --> Aug 2025

3 months ago

Trial primary completion date

RAD51B (RAD51 Paralog B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • RAD54L (DNA Repair And Recombination Protein RAD54)

ATRX mutation • RAD54L mutation • RAD51 mutation

Lynparza (olaparib) • carboplatin

3ms

PARPi-PANC: Niraparib As First Line Therapy with Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)

P2, N=0, Withdrawn, Centre Leon Berard | N=28 --> 0 | Recruiting --> Withdrawn

3 months ago

Enrollment change • Trial withdrawal • Metastases

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)

HRD signature

Zejula (niraparib)

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

Real-world prevalence of homologous recombination repair (HRR) gene mutations in advanced breast (ABC) and selected gastrointestinal cancers (GIC) using comprehensive next-generation sequencing (NGS) assays in Asia and the Middle East (AME) (ESMO Asia 2024)

For cfDNA: Detection rates of NCCNr and HRRm were similar to those reported for tissue-based NGS in analyzed cancer types. Conclusions Mutations in HRR genes can be successfully analyzed using either tumor tissue or cfDNA NGS.

3 months ago

Clinical • Real-world evidence • Next-generation sequencing • BRCA Biomarker • Real-world • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D)

BRAF V600E • KRAS G12C • BRAF V600 • KRAS G12 • FANCA mutation

Guardant360 TissueNext™

3ms

Mechanism of BCDX2-mediated RAD51 nucleation on short ssDNA stretches and fork DNA. (PubMed, Nucleic Acids Res)

Moreover, while mutants defective in ssDNA binding retain the ability to bind branched DNA substrates, they still facilitate RAD51 loading onto reversed replication forks. Our study provides mechanistic insights into how the BCDX2 complex stimulates the formation of BRCA2-independent RAD51 filaments on short stretches of ssDNA present at ssDNA gaps or stalled replication forks, highlighting its role in genome maintenance and DNA repair.

3 months ago

Journal • BRCA Biomarker

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

Germline genetic mutations in a multi-center cohort of 248 phyllodes tumors. (PubMed, Breast Cancer Res Treat)

Our study demonstrates that 7.7% of women with PT harbor germline P/LP variants in genes associated with AD cancer conditions. Early identification of these variants has implications for screening, risk reduction, and/or treatment. National guidelines for women with PT do not currently address germline genetic testing, which could be considered.

3 months ago

Journal

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

RAD51D 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

4ms

Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer. (PubMed, JAMA Netw Open)

In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

4 months ago

Journal • BRCA Biomarker • PARP Biomarker

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1)

4ms

Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families. (PubMed, J Pers Med)

Taking the family studies in our registry and tumor molecular pathology together, we concluded that this relatively common RAD51D variant showed incomplete penetrance in our local Chinese community. Personalized genetic counseling emphasizing family history for families with this variant, as suggested at the UK Cancer Genetics Group (UKCGG) Consensus meeting, would also be appropriate in Chinese families.

4 months ago

Journal

HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

4ms

Investigating the impact of adding olaparib, or olaparib and durvalumab together, to standard chemotherapy before surgery in young, pre-menopausal women with HER2-negative breast cancer. (ACTRN12623000657628)

P2, N=56, Recruiting, Breast Cancer Trials | Not yet recruiting --> Recruiting

4 months ago

Enrollment open

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D)

Lynparza (olaparib) • Imfinzi (durvalumab) • paclitaxel

4ms

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: Dec 2026 --> Jul 2026 | Trial primary completion date: Dec 2026 --> Jul 2026

4 months ago

Trial completion date • Trial primary completion date • Combination therapy • Metastases

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

4ms

The Clinical and Genetic Landscape of Hereditary Cancer: Experience from a Single Clinical Diagnostic Laboratory. (PubMed, Cancer Genomics Proteomics)

Comprehensive multigene genetic testing is necessary for appropriate clinical management of pathogenic variants' carriers. Additionally, the information obtained is important for determining the risk of malignancy development in family members of the examined individuals.

4 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) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)

4ms

Marginal Contribution of Pathogenic RAD51D Germline Variants to Pakistani Early-Onset and Familial Breast/Ovarian Cancer Patients. (PubMed, J Cancer Allied Spec)

No pathogenic RAD51D variant was identified in the current study. Our study data suggested a negligible association of RAD51D variants with BC/OC risk in Pakistani women.

4 months ago

Journal

RAD51D (RAD51 paralog D)

4ms

The Impact of Li Fraumeni and Germline Retinoblastoma Mutations on Leiomyosarcoma Initiation, Outcomes and Genetic Testing Recommendations. (PubMed, Clin Cancer Res)

While ULMS patients had a relatively low proportion of PGV, a high percentage of STLMS patients with PGV had tumor biallelic status, indicating that PGV drive tumorigenesis in these individuals. These findings have significant implications for genetic testing recommendations.

4 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51D (RAD51 paralog D)

MSK-IMPACT

4ms

Avelumab and M6620 for the Treatment of DDR Deficient Metastatic or Unresectable Solid Tumors (clinicaltrials.gov)

P1/2, N=25, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2024 --> Dec 2025 | Trial primary completion date: Sep 2024 --> Dec 2025

4 months ago

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) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CD4 (CD4 Molecule) • 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)

Bavencio (avelumab) • berzosertib (M6620)

4ms

Four cancer cases with pathological germline variant RAD51D c.270_271dup. (PubMed, J Obstet Gynaecol Res)

The current spread of cancer genomic analysis will increase opportunities for incidental variant identification. The establishment of Japanese guidelines is expected to aid in the management of PGV carriers of moderate-risk genes.

4 months ago

Journal

RAD51D (RAD51 paralog D)

4ms

Landscape of homologous recombination deficiency in gastric cancer and clinical implications for first-line chemotherapy. (PubMed, Gastric Cancer)

Low proportion of macroscopic type 3 or 4 tumors and a high TMB are distinctive features of GC with HRD. HRD status is a potential predictive marker in platinum-based first-line chemotherapy for unresectable metastatic GC.

4 months ago

Journal • BRCA Biomarker • PARP 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) • RAD51 (RAD51 Homolog A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • WRN (WRN RecQ Like Helicase) • XRCC2 (X-Ray Repair Cross Complementing 2)

4ms

Using polygenic risk modification to improve breast cancer prevention: study protocol for the PRiMo multicentre randomised controlled trial. (PubMed, BMJ Open)

Study findings will be disseminated via peer-reviewed publications and conference presentations, and directly to participants. ACTRN12621000009819.

4 months ago

Clinical protocol • Journal • BRCA Biomarker

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)