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BIOMARKER:

HRD + BRCA1 mutation

i
Other names: BRCA1, BRCC1, PPP1R53, RNF53, Breast cancer 1, early onset, HRD, Homologous Recombination Deficiency
Entrez ID:
Related biomarkers:
21h
Potential value of the homologous recombination deficiency signature we developed in the prognosis and drug sensitivity of gastric cancer. (PubMed, Front Genet)
Relationship between the risk model and patient survival, BRCA1, BRCA2 mutation, response to Cisplatin and Talazoparib treatment was analyzed by generating Kaplan-Meier curve, mutations waterfall map and conducting Pearson correlation analysis. The risk score of adrenocortical carcinoma (ACC), stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), kidney renal clear cell carcinoma (KIRC), sarcoma (SARC), prostate adenocarcinoma (PRAD), breast invasive carcinoma (BRCA) was significantly positively correlated with HRD score. We developed an 11 HRD scores-related genes risk model and revealed the potential association between HRD status and GC prognosis, gene mutations, patients' sensitivity to therapeutic drugs.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • BRCA (Breast cancer early onset) • MAGEE1 (MAGE family member E1) • IGFBP1 (Insulin Like Growth Factor Binding Protein 1)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • HRD signature
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cisplatin • Talzenna (talazoparib)
13d
Reversion mutations in germline BRCA1/2-mutant tumors reveal a BRCA-mediated phenotype in non-canonical histologies. (PubMed, Nat Commun)
Whole exome sequencing confirms the homologous recombination deficiency phenotype of these tumors. While reversion mutations arise in all BRCA-associated cancer types, here we show that reversion mutations arising post-platinum in non-BRCA associated histologies, while rare, may indicate BRCA1/2 mediated tumorigenesis.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
17d
Molecular intrinsic subtypes, genomic, and immune landscapes of BRCA-proficient but HRD-high ER-positive/HER2-negative early breast cancers. (PubMed, Breast Cancer Res)
This study highlights possible novel biological differences among ER + /HER2- breast cancer related to HRD status. Our results could have important implications for translational research and/or the design of future clinical trials, but require prospective clinical evaluation.
Journal • BRCA Biomarker
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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) • BRCA (Breast cancer early onset)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • ER positive • HER-2 negative • HER-2 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation • ER positive + HER-2 negative • High HRD score
22d
Development of a novel BRCAness score that predicts response to PARP inhibitors. (PubMed, Biomark Res)
We established a novel BRCAness score using BRCA-mutation-related gene expressions and found that it associates with DNA repair and predicts response to PARP inhibitors regardless of BRCA mutation.
Journal • Tumor Mutational Burden • BRCA Biomarker • PARP Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • MKI67 (Marker of proliferation Ki-67)
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HER-2 positive • BRCA1 mutation • ER positive • HER-2 negative • HRD • HRD + BRCA1 mutation • BRCA mutation • ER positive + HER-2 negative
22d
Human metastatic cholangiocarcinoma patient-derived xenografts and tumoroids for preclinical drug evaluation. (PubMed, Clin Cancer Res)
Our results suggest that advanced CCA patients with pathogenic mutations of BRCA2, but not those with mutations of IDH1, ARID1A, or BAP1, are likely to benefit from PARPi therapy. This collection of CCA_PDXs provides new opportunities for evaluating drug response and prioritizing clinical trials.
Preclinical • Journal • BRCA Biomarker • PARP Biomarker
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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) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1) • RAD51 (RAD51 Homolog A)
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BRCA2 mutation • BRCA1 mutation • IDH1 mutation • HRD • ARID1A mutation • BAP1 mutation • HRD + BRCA1 mutation • RAD51 mutation
1m
Homologous Recombination DNA Repair Deficiency Score Is Independent Prognostic Variable in Myelodysplastic Syndrome/ Acute Myeloid Leukemia with Complex Karyotype (ASH 2022)
CK-AML/MDS cases with TP53 mutations have a significantly higher HRD score compared to those with wild-type TP53. HRD score is an independent prognostic biomarker with a potential therapeutic opportunity for treatment using DNA damaging drugs.
BRCA Biomarker • PARP Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • RAD51C (RAD51 paralog C) • DRD (DNA Repair Deficiency)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • HRD • TP53 wild-type • DDR • PALB2 mutation • RAD51C mutation • RAD51D mutation • HRD + BRCA1 mutation • DRD • RAD51 mutation • High HRD score
1m
Alterations in Homologous Recombination-Related Genes and Distinct Platinum Response in Metastatic Triple-Negative Breast Cancers: A Subgroup Analysis of the ProfiLER-01 Trial. (PubMed, J Pers Med)
Regarding group B, patients with disease control exhibited mutations in FANCL, FANCA and the RAD51D genes or RAD51C methylation; mutations in HRR genes and epimutations in RAD51C were associated with disease control through platinum-based chemotherapy. As such, apart from well-characterized alterations in BRCA1/2, a more comprehensive evaluation of HRD should be considered in order to enlarge the selection of patients with mTNBC that could benefit from platinum-based chemotherapy.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • FANCA (FA Complementation Group A) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • FANCL (FA Complementation Group L)
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BRCA2 mutation • BRCA1 mutation • HRD • FANCA mutation • RAD51D mutation • HRD + BRCA1 mutation • BRCA1 hypermethylation • RAD51 mutation
1m
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset)
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BRCA2 mutation • BRCA1 mutation • HRD + BRCA1 mutation
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AiTan (rivoceranib)
1m
Maintenance therapy with a poly(ADP-ribose) polymerase inhibitor in patients with newly diagnosed advanced epithelial ovarian cancer: individual patient data and trial-level meta-analysis. (PubMed, ESMO Open)
Among newly diagnosed ovarian cancer patients, PARPi maintenance therapy significantly improves PFS in those with germline and/or somatic BRCA mutation and/or HRD-positive tumor but not in those with HRD-negative tumor.
Retrospective data • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
1m
Comprehensive Profiling of Copy Number Changes to Assess Genomic Instability (AMP 2022)
Recently, the sensitivity of certain cancers to DNA damaging therapeutics such as cisplatin and inhibitors of poly (ADP-ribose) polymerase has been associated with HRD... We developed a novel method to determine genomic instability using OCA Plus, which was developed for fast comprehensive genomic profiling of cancer FFPE samples to aid research into precision oncology. By combining genomic instability assessment with DNA repair pathway analysis, OCA Plus will support research into the mechanisms underlying HRD.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
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cisplatin
2ms
Genomic and expressional dynamics of ovarian cancer cell lines in PARPi treatment revealed mechanisms of acquired resistance. (PubMed, Gynecol Oncol)
Long-term PARPi treatment led to evolutionary genomic and transcriptional alterations that were associated with acquired resistance, among which depressed EP300 partly contributed to the resistant phenotype.
Preclinical • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDH1 (Cadherin 1) • EP300 (E1A binding protein p300)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
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Lynparza (olaparib)
2ms
Deep-Learning to Predict BRCA Mutation and Survival from Digital H&E Slides of Epithelial Ovarian Cancer. (PubMed, Int J Mol Sci)
Based on these analyses, we have planned further steps of development such as proving a reference classification performance, exploring the hyperparameters space for training optimization, eventually tweaking the learning algorithms and the neural networks architecture for better suiting this specific task. These actions may allow the model to improve performances for all the considered outcomes.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
2ms
PARP Inhibitors in Advanced Prostate Cancer in Tumors with DNA Damage Signatures. (PubMed, Cancers (Basel))
While the sensitivity of PARPi in tumors with non-BRCA DNA damage signatures is not as well established, it has been suggested that genomic alterations in DNA damage repair (DDR) genes other than BRCA may confer synthetic lethality with PARPI in mCRPC. The aim of this review is to summarize the literature on PARPi and their activity treating BRCA and non BRCA tumors with DNA damage signatures.
Review • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
2ms
Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in triple negative breast cancer and ovarian carcinoma (SABCS 2022)
A cohort of 43 PDX models of TNBC was genomically characterized and responses to both single agent platinum and docetaxel were evaluated in vivo...On the other end, a high immune transcriptional signature identifies patients with BRCA proficient cancers that are more likely to benefit from platinum therapy. Taken together, our study underscores the importance of characterizing molecular heterogeneity to optimize predictive precision in assigning response probabilities in TNBC and OvCa.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA1 expression • BRCA mutation
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docetaxel
3ms
A comprehensive literature review and meta-analysis of the prevalence of pan-cancer BRCA mutations, homologous recombination repair gene mutations, and homologous recombination deficiencies. (PubMed, Environ Mol Mutagen)
The prevalence of HRD positivity was 56% overall (95% CI = 48%-64%). The understanding of biomarker prevalence across tumor types and standardization of biomarker assays could have important clinical implications.
Retrospective data • Review • Journal • BRCA Biomarker • PARP Biomarker • Pan tumor
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • CHEK2 mutation • HRD + BRCA1 mutation • BRCA mutation
3ms
BRCA1/2 MUTATIONS AND SECONDARY CYTOREDUCTIVE SURGERY AS GOOD PROGNOSTIC FACTORS IN PARP INHIBITOR USERS WITH RECURRENT OVARIAN CANCER (IGCS 2022)
Our results suggest that BRCA1/2 mutation including VUS and secondary cytoreductive surgery might be associated with longer PFS in ovarian cancer patients who use PARP inhibitor.
BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
3ms
Case report: Response to platinum agents and poly (adenosine diphosphate-ribose) polymerase inhibitor in a patient with BRCA1 c.5096G>A (R1699Q) intermediate-risk variant. (PubMed, Cancer Treat Res Commun)
This is the first report of the clinical outcome of PARP inhibitor and platinum-containing chemotherapy in a patient with a BRCA1 R1699Q variant. Despite BRCA1 mutation and high GIS, used as indicators of drug sensitivity, the recurrent tumor did not respond well to platinum agents and olaparib. BRCA1 R1699Q variant could differ from others in cancer risk and in drug response. Further studies are needed to confirm these observations.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA1 mutation • HRD • HRD + BRCA1 mutation
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BRACAnalysis CDx™ • Myriad myChoice® CDx
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Lynparza (olaparib)
3ms
HOMOLOGOUS RECOMBINATION DEFICIENCY AND CYCLIN E1 AMPLIFICATION ARE CORRELATED WITH IMMUNE CELL INFILTRATION AND SURVIVAL IN HIGH-GRADE SEROUS OVARIAN CANCER (IGCS 2022)
Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profile and TME which could assist with patienttailored treatment in the future.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CD20 (Membrane Spanning 4-Domains A1) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • BRCA (Breast cancer early onset) • ITGAE (Integrin Subunit Alpha E)
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BRCA2 mutation • BRCA1 mutation • HRD • CCNE1 amplification • HRD + BRCA1 mutation • CCNE1 mutation
4ms
Évolution des traitements adjuvants des cancers de l'ovaire (PubMed, Rev Prat)
Standard of care remains first-line chemotherapy -with the 3 weekly association carboplatin- paclitaxel-, with or without bevacizumab after surgery. Poly-(ADP-ribose) polymerase inhibitors (PARPi) are indicated as maintenance treatment from the first line of advanced forms (FIGO stages III and IV) with BRCA1 or BRCA2 mutation following partial or complete response to chemotherapy (olaparib ou niraparib), when there is no indication for bevacizumab; they are also indicated as maintenance treatment with olaparib associated to bevacizumab in patients whose HRD test (homologous recombination deficiency : DNA repair defect by homologous recombination) is positive (with or without BRCA mutation) and have an indication for bevacizumab. In case of contraindication or no indication for bevacizumab, niraparib can also be used alone for 3 years after response to chemotherapy, whatever the HR status.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
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Avastin (bevacizumab) • Lynparza (olaparib) • carboplatin • paclitaxel • Zejula (niraparib)
4ms
Frequency and clinical significance of homologous recombination deficiency gene mutations in non-cutaneous melanoma (ESMO 2022)
The 1-year, 3-year and 5-year survival rates were 92.8%, 63.8%, 55.6%, respectively. Conclusions ATM and ARID1A are the most common genomic alterations with HRR genes and patients with HRR gene mutations maybe get survival benefits from treatment.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • PALB2 (Partner and localizer of BRCA2) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • ARID2 (AT-Rich Interaction Domain 2) • RAD50 (RAD50 Double Strand Break Repair Protein)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • HRD • ARID1A mutation • PALB2 mutation • HRD + BRCA1 mutation
4ms
Ki67 as a predictor of response to PARP inhibitors in platinum sensitive BRCA wild type ovarian cancers: MITO 37 retrospective study (ESMO 2022)
Clinical data were collected from all pts with high grade serous or endometroid BRCA WT OC treated with niraparib or rucaparib maintenance between 2010-2021. Conclusions Preliminary results show that high Ki-67 at diagnosis potentially discriminates among BRCA WT responders to PARPi. Further analyses are ongoing.
Retrospective data • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type • HRD + BRCA1 mutation
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Rubraca (rucaparib) • Zejula (niraparib)
5ms
Genomic and epigenomic BRCA alterations predict adaptive resistance and response to platinum-based therapy in patients with triple-negative breast and ovarian carcinomas. (PubMed, Sci Transl Med)
We showed how integrating both this cancer immune signature and the presence of BRCA mutations results in more accurate predictions of patient response when compared to either HRD status or BRCA status alone. This underscores the importance of defining BRCA heterogeneity in optimizing the predictive precision of assigning response probabilities in TNBC and OvCa.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • BRCA1 mutation + BRCA2 mutation • HRD + BRCA1 mutation • BRCA1 expression • BRCA mutation
5ms
Olaparib treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency status: Phase II LIGHT study primary analysis. (PubMed, Gynecol Oncol)
Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies.
Clinical • P2 data • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
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BRACAnalysis CDx™ • Myriad myChoice® CDx
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Lynparza (olaparib)
5ms
Phase II study of niraparib in recurrent or persistent rare fraction of gynecologic malignancies with homologous recombination deficiency (JGOG2052). (PubMed, J Gynecol Oncol)
The sample size is 16-20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate. Japan Primary Registries Network (JPRN) Identifier: jRCT2031210264.
P2 data • Review • Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
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Zejula (niraparib)
5ms
Combinations of ATR, Chk1 and Wee1 inhibitors with olaparib shows synergistic effect in olaparib resistant Brca1 deficient murine ovarian cell lines. (EACR 2022)
Conclusion We generated an olaparib resistant cell lines deficient in HR with multiple mechanisms of resistance. In both resistant and parental sublines, the combination of olaparib with different DDR inhibitors showed a synergistic effect.
Preclinical • BRCA Biomarker • PARP Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
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Lynparza (olaparib)
5ms
Deep learning predicts somatic BRCA 1/2 genes mutational status from histopathology of epithelial ovarian cancer: a hypothesis generating study (EACR 2022)
On the one hand, we are already exploring the hyperparameters space for training optimization, eventually tweaking the learning algorithms and the neural networks architecture for better suiting the task of somatic BRCA 1/2 status identification. On the other, we are also adopting on the same dataset a different approach based on persistent homology.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA mutation
6ms
Retrospective Analysis of BRCA1/2 Alterations in Advanced NSCLC Using An Amplicon-based NGS Liquid Biopsy Assay (IASLC-WCLC 2022)
Ultrasensitive liquid biopsy enables detection of pathogenic BRCA1/2 alterations in plasma cfDNA of lung adenocarcinomas, despite low VAFs. Retrospective analysis suggests a difference in cfDNA mutational profiles in BRCA1/2 mutants, warranting further investigation on the role of BRCA1/2, HRD, and correlation with ICI treatment response in lung adenocarcinoma.
Retrospective data • BRCA Biomarker • IO biomarker • Liquid biopsy • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • BRAF mutation • HRD • MET mutation • BRCA wild-type • BRCA2 deletion • BRCA1 deletion • HRD + BRCA1 mutation • BRCA mutation • BRCA1 positive • BRCA2 positive
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LiquidHALLMARK®
6ms
Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A) • BRCA (Breast cancer early onset)
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HER-2 positive • BRCA2 mutation • BRCA1 mutation • HR positive • HER-2 negative • HRD • BRCA wild-type • HR positive + HER-2 negative • HRD + BRCA1 mutation
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Zejula (niraparib)
6ms
Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer (clinicaltrials.gov)
P2, N=18, Recruiting, Academic and Community Cancer Research United | Active, not recruiting --> Recruiting | Trial primary completion date: Aug 2021 --> Aug 2023
Enrollment open • Trial primary completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation
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Rubraca (rucaparib) • leucovorin calcium • Onivyde (nanoliposomal irinotecan) • fluorouracil topical
6ms
Upregulation of CXCL1 and LY9 contributes to BRCAness in ovarian cancer and mediates response to PARPi and immune checkpoint blockade. (PubMed, Br J Cancer)
In conclusion, 2-GPS could robustly predict BRCAness OvCa at the individual level and extend the population who may benefit from PARP inhibitors.
Journal • Checkpoint inhibition • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • LY9 (Lymphocyte Antigen 9) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
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BRCA2 mutation • BRCA1 mutation • HRD • LY9 expression • HRD + BRCA1 mutation
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Lynparza (olaparib) • cisplatin • mitomycin
7ms
Testing of newly diagnosed advanced high grade ovarian cancer (OC) patients with the Myriad Genetics MyChoice CDx Plus next generation sequencing-based in vitro diagnostic test emphasizes the need for public insurance coverage of genetic testing: Results of a national program by the Hellenic Society of Medical Oncology (HeSMO). (ASCO 2022)
In our series, 48.46% of the patients with high grade OC tested as BRCA1/2 and/or GIS positive, in accordance with published data, underlying the clinical need to implement GIS testing in OC patients’ molecular evaluation. Apart from the significant implications for treatment possibilities in an expanded patients’ population, these results are important for cancer prevention. We strongly believe that our results will strengthen our efforts for reimbursement of such testing in high grade OC patients, and will serve as a roadmap for the establishment of local HRD testing solutions.
Preclinical • Reimbursement • Next-generation sequencing • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • FANCL (FA Complementation Group L)
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BRCA2 mutation • BRCA1 mutation • HRD • PALB2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • HRD + BRCA1 mutation
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Myriad myChoice® CDx
7ms
Analytical evaluation of a commercial in-house homologous recombination deficiency (HRD) assay for patients with epithelial ovarian cancers and its concordance with a reference standard. (ASCO 2022)
The HRD status assessed by AmoyDx HRD Focus Panel is highly concordant with that obtained using the current standard reference method. Commercial in-house test may offer a cost-effective, reliable and robust alternative to the centralized assay for the evaluation of HRD status in patient with EOC.
Clinical • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation
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Myriad myChoice® CDx • AmoyDx® HRD Focus Panel
7ms
Homologous recombination deficiency predicts response to platinum-based neoadjuvant chemotherapy in early-stage triple-negative breast cancer patients: Secondary analysis of the neocart randomized clinical trial. (ASCO 2022)
Background: We recently performed the NeoCART trial to compare six cycles of docetaxel plus carboplatin (DCb) with four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel (EC-D) in the neoadjuvant setting of triple-negative breast cancer (TNBC). PCR in TNBC patients correlated with a higher HRD score, higher stromal TILs, and a higher Ki67 index on carboplatin-based neoadjuvant chemotherapy regardless of BRCA status.
Clinical • BRCA Biomarker
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • High HRD score
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carboplatin • docetaxel • cyclophosphamide • epirubicin
7ms
Impact of tumor percentage on the assessment of homologous recombination deficiency score using a NGS 523 gene panel and a cytogenetic software in the evaluation of epithelial ovarian tumors. (ASCO 2022)
HRD correlates with platinum sensitivity in epithelial ovarian tumors, which has clinical significance as a predictor of sensitivity to PARPi. During treatment, tissue samples are obtained at different times points and sources, some at diagnosis/surgical debulking and some after neoadjuvant therapy. After neoadjuvant treatment, tumor volume is reduced.
Next-generation sequencing • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • High HRD score
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TruSight Oncology 500 Assay
7ms
Characterization of mutational signatures of homologous recombination deficiency (HRD) in Chinese breast cancer. (ASCO 2022)
This study comprehensively delineated the genetic characteristics of HRD tumors, which suggests that HRD status marked by HRD score is strongly associated with BRCA1/2 and HR-related genes mutation as well as other genomic instability signatures, thus indicating its predictive value as a promising biomarker for DNA repair deficiency related drugs or therapies in Chinese breast cancer.
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) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • DRD (DNA Repair Deficiency)
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BRCA2 mutation • BRCA1 mutation • HER-2 amplification • HER-2 negative • HRD • DDR • BRCA wild-type • HRD + BRCA1 mutation • BRCA mutation • NBN mutation • DRD
7ms
Liposomal Irinotecan, Fluorouracil, Leucovorin Calcium, and Rucaparib in Treating Patients With Metastatic Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer (clinicaltrials.gov)
P2, N=18, Active, not recruiting, Academic and Community Cancer Research United | N=110 --> 18 | Trial completion date: Jul 2026 --> Aug 2025
Enrollment change • Trial completion date
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset)
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BRCA2 mutation • BRCA1 mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation
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Rubraca (rucaparib) • leucovorin calcium • Onivyde (nanoliposomal irinotecan) • fluorouracil topical
8ms
PTEN Loss and BRCA1 Promoter Hypermethylation Negatively Predict for Immunogenicity in BRCA-Deficient Ovarian Cancer. (PubMed, JCO Precis Oncol)
Our study suggests that within ovarian cancers with genetic loss of BRCA1/2 are two subsets exhibiting differential immunogenicity, with lower levels associated with PTEN loss and BRCA hypermethylation. These genomic features of BRCA1/2-associated ovarian cancers may inform considerations around how to optimally deploy immune checkpoint inhibitors in the clinic.
Journal • Tumor Mutational Burden • BRCA Biomarker • IO biomarker
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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRD (Homologous Recombination Deficiency) • CD8 (cluster of differentiation 8) • BRCA (Breast cancer early onset) • FOXP3 (Forkhead Box P3) • PRF1 (Perforin 1)
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BRCA2 mutation • BRCA1 mutation • HRD • HRD + BRCA1 mutation • BRCA1 hypermethylation • High HRD score
9ms
Treatment patterns after poly-ADP ribose polymerase (PARP) inhibitors in epithelial ovarian cancer patients. (PubMed, Int J Gynecol Cancer)
Platinum doublet chemotherapy resulted in non-significant improved progression-free survival compared with other regimens, suggesting potential independent mechanisms of resistance between PARP inhibitor and platinum compounds.
Journal • BRCA Biomarker • PARP Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA2 mutation • BRCA1 mutation • HRD • BRCA wild-type • HRD + BRCA1 mutation
9ms
Comprehensive Analysis of Somatic Reversion Mutations in Homologous Recombination Repair (HRR) Genes in A Large Cohort of Chinese Pan-cancer Patients. (PubMed, J Cancer)
The results revealed that reversion mutations frequently occurred after resistance to platinum-based chemotherapy and/or PARP inhibitor. Our study provides insight into the underlying mechanism of drug resistance in HRD tumors and suggests that monitoring HRR mutation status along the disease course could be beneficial especially for informing resistance mechanisms and guiding subsequent therapies.
Journal • BRCA Biomarker • PARP Biomarker • Pan tumor
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2)
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BRCA1 mutation • HRD • PALB2 mutation • HRD + BRCA1 mutation
9ms
Toward More Comprehensive Homologous Recombination Deficiency Assays in Ovarian Cancer, Part 1: Technical Considerations. (PubMed, Cancers (Basel))
In these companion reviews, we review and present evidence to date regarding HRD definitions, achievements and limitations in HGSOC. Part 1 is dedicated to technical considerations and proposed perspectives that could lead to a more comprehensive and dynamic assessment of HR, while Part 2 provides a more integrated approach for clinicians.
Review • Journal • BRCA Biomarker • PARP Biomarker • BRCA Companion diagnostic • PARP Companion diagnostic
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency)
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BRCA2 mutation • BRCA1 mutation • HRD • BRCA1 mutation + BRCA2 mutation • HRD + BRCA1 mutation
9ms
Mutation profiling of homologous recombination-related (HRR) genes in sarcoma patients (AACR 2022)
Our results reported the genetic landscape of HRR genes in Chinese sarcoma patients, providing a reference for the clinical application of PARP inhibitors.
Clinical • Tumor Mutational Burden • BRCA Biomarker • PARP Biomarker
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TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler) • FANCA (FA Complementation Group A)
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BRCA2 mutation • BRCA1 mutation • HRD • FANCA mutation • BRCA1 mutation + BRCA2 mutation • HRD + BRCA1 mutation
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Onco PanScan™
9ms
Effects of homologous recombination-related gene mutation subtypes on gene instability and the efficacy of platinum-containing regiments in triple-negative breast cancer (AACR 2022)
In this study, we found that different HR-related genes mutation subtypes may exert distinct effects on genomic instability, and mutations in HR-related genes beyond the context of BRCA1/2 may serve as a biomarker for platinum-based adjuvant therapy for TNBC patients, which warrants further studies.
Clinical • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • HRD • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • HRD + BRCA1 mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • CHEK1 mutation • CHEK1 expression • High HRD score