BRCA1 mutation + BRCA2 mutation

One in three women showed a pathogenic mutation, demonstrating a significant prevalence of germline mutations in this sample. Additionally, the small sample revealed an interesting number of mutations, indicating the need to explore more regions of the country.

P1, N=150, Active, not recruiting, Nerviano Medical Sciences | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024

P2, N=123, Active, not recruiting, National Cancer Institute (NCI)

Having a higher BC risk status does not result in better adherence to the risk management program. However, factors directly related to screening rounds reduced postponements. Future research should address the benefits of screening-related organizational factors that contribute to adherence improvement.

For Southern Indian patients, a two-tiered approach can be considered: Initial screening with ASPCR for BRCA1 185delAG followed by NGS for those testing negative. Expanding the gene panel and identifying other population-specific mutation hot spots is a promising area with potential for improvements in testing and treatment strategies.

The present study reveals unique BRCA1 and BRCA2 mutations in Pakhtun population. We further suggest sequencing of the large cohorts for further characterizing the pathogenic mutations.

The identification of BRCA1/2 alterations in ctDNA could guide the use of germline testing. The VAF cutoff identified for the likelihood of a germinal mutation is lower than expected, suggesting that a wider population should be screened for germinal mutation with relevant impact on the therapeutic choices and family screening.

P1/2, N=384, Recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jan 2024 --> Dec 2024

P=N/A, N=609, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

These yet-to-be-discovered mechanisms, while purely speculative, may be valuable to understanding human breast cancer, though they may not be exclusive to the mammary gland epithelial cells. Combining these themes, we review some anti-carcinogenesis preventive strategies and prospects of new interventions against breast cancer.

A total of eight CNVs in BRCAs were detected from the 293 samples, and the molecular breakpoints were successfully identified in five samples through long-range PCR followed by Sanger sequencing. Our results suggested that MS assay might be an effective method in primary screening for CNVs in genes such as BRCAs, especially when short turnaround time and/or high sensitivity is a top priority.

In conclusion, our study reveals the unique genetic profile of HNSC in Pakistani patients, featuring unique pathogenic mutations in BRCA1 and BRCA2 genes. These mutations offer promise as valuable diagnostic markers and potential therapeutic targets.

The majority of patients from this real-world dataset underwent FoundationOneCDx testing after initiation of first-line treatment. Testing appeared to influence treatment patterns, with a higher proportion of patients with BRCAm, HRRm, and HRD-positive disease receiving PARP inhibitors.

It will review the current evidence-based imaging recommendations for different modalities and ages of screening initiation in screening this patient population at high risk. Special considerations in transgender BRCA1 and BRCA2 mutation carriers are also discussed.

P=N/A, N=13320, Active, not recruiting, Memorial Sloan Kettering Cancer Center

Testing positive for a BRCA PV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively.

Thus, our studies provide a high-resolution transcriptome atlas of breast epithelial cells of BRCA1 and BRCA2 mutation carriers and reveal their susceptibility to PIK3CA mutation-driven transformation.  .

Responses were observed in patients without germline or somatic BRCA1/2 mutations, including patients with mutations in other homologous recombination repair genes and tumours with functional homologous recombination deficiency by RAD51 foci. Conclusion The response rate to olaparib and ceralasertib did not meet pre-specified criteria for activity in the overall evaluable population, but responses were observed in patients who would not be expected to respond to Olaparib monotherapy.

Knowledge of the spectrum and frequency of mutations in BRCA1 and BRCA2 genes predisposing to breast cancer, which are present in varying frequencies in the Kazakh population, will provide a more effective approach to the screening protocol and allow for a faster, less expensive and more accessible genetic testing strategy for the Kazakhstan citizens.

No partial or total nipple necrosis occurred. NSM is safe for reducing the risk of BC development in BRCA mutation carriers and for treating cancer.

Consistently detecting clinically significant the HRD status in PDAC has remained challenging with current commercially available platforms. Multiple novel HRD-targeted therapies for PDAC are currently in development and clinical trials, offering new opportunities for these patients.

P=N/A, N=2700, Not yet recruiting, AstraZeneca

In all cases, the associated DCIS shows the same pattern of expression as the invasive carcinoma, suggesting that overexpression occurs early in tumorigenesis, while tumor cells are still confined within the ducts. The high rate of overexpression of EZH2 in BRCA1- and BRCA2-associated tumors suggests a potential role for EZH2 as a target and/or a biomarker in these cancers.

The prevalence of BRCA1/2 mutations in the African American and Latina population is higher than what was observed in White women. These data provide additional support for the recommendation to perform germline testing in all women with breast cancer, regardless of race or ethnicity

More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than non-carrier breast tissues with more integrin receptor-expressing stromal cells. These results reveal alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.

Therefore, the formulation of effective treatment strategies to overcome resistance to PARPis is urgently necessary. This review summarizes the molecular mechanism of therapeutic action and resistance to PARPis, in addition to emerging combination treatment options involving PARPis.

More integrin-ligand pairs were differentially correlated in BRCA1/2-mutant breast tissues than non-carrier breast tissues with more integrin receptor-expressing stromal cells. Implications: These results suggest alterations in the communication between mammary epithelial cells and the microenvironment in BRCA1 and BRCA2 mutation carriers, laying the foundation for designing innovative breast cancer chemo-prevention strategies for high-risk patients.

Overall, the cost-per-cycle for PROC treatment ranged from $53 to $4,360 for chemotherapy, $6,989 to $9,806 for bevacizumab, and $7,780 to $9,022 for poly- (adenosine diphosphate-ribose) polymerase inhibitors (Figure 1). A total of 19 records from 18 studies were included, two of which were US cost-effectiveness analyses (CEAs) from the updated SLR. A 2022 US CEA reported that olaparib was cost-effective vs niraparib for BRCA1 and BRCA2-mutation-positive PROC at a willingness-to-pay threshold of $100,000. In another CEA from 2022, total parenteral nutrition was not cost-effective for the management of inoperable malignant bowel obstruction in PROC.

The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.

In this review, we decipher the relationship between BRCA1/2 alterations and genomic instability leading to gynecomammary cancers through results from patients, mice, and cell lines. Understanding the early events of BRCA1/2-driven genomic instability in gynecomammary cancers would help to find new biomarkers for early diagnosis, improve the sensitivity of emerging therapies such as PARP inhibitors, and reveal new potential therapeutic targets.

When applied to transcript expression data from high-risk families grouped by mutation status, Tetris reveals the features and pathways characterizing each group and the sharing patterns among them. Finally, we further extend Tetris to discover groupings of samples when group labels are not provided, which can elucidate additional structure in these data.

In spite of pre-clinical data demonstrating increased radiosensitivity for BRCA1/2-mutated BC cells lines, this large, previously unexamined dataset found BRCA1/2 mutations did not predict an improved OS or DFS for patients who received RT. When compared with WT BRCA patients, patients with BRCA1/2 mutations were found to have tumors of higher grade and clinical stage and to undergo more mastectomies. In a comparison with BRCA2-mutated patients, patients with mutations of BRCA1 were younger, more often ER/PR negative, and more likely to have high-stage tumors. The survival data and the advanced stage of BRCA1/2-mutated tumors suggest that the effect of BRCA1/2 mutations on radiosensitivity in vitro may be nullified by the aggressive behavior of BRCA1/2-mutated tumors in vivo.

our study revealed BRCA mutations that could be common among our population. Further, it has shown that BRCA1 and BRCA2 genetic mutations identified are of clinical relevance and there is a need to screen for these mutations in breast cancer patients to understand their implication in patient management outcomes.

The reported prevalence was highly variable among the small-sized published studies that adopted adequate techniques. In our patient cohort, there was a high incidence of VUS in BRCA1/2 genes. Accordingly, there is an actual demand to conduct a prospective well-designed national study to accurately estimate the prevalence of BRCA1/2 mutations among patients with BC in Egypt.

Here we provide an overview of the findings and the ongoing debate regarding BRCA haploinsufficiency. We further put out the challenges in studying this topic and discuss its potential relevance in the prevention and treatment of BRCA-related cancers.

Patients with BRCA1 mutations are more benefit from platinum-regimen. The value of platinum-regimen for early breast cancer patients with BRCA1 and BRCA2 needs to be verified further.

BRCA genes are one of the genes that may increase the risk of developing colorectal cancer. Thus, BRCA genes could be potential candidates that may be included in the colorectal cancer genetic testing panel.

While payers define high risk based on the CPS + EG score from the OlympiA trial, HCPs adopt a broader definition including genomic risk scores, lymph node involvement, and tumor grade and size. A dialogue to harmonize risk classification and testing eligibility across stakeholders is critical to address this disconnect and increase gBRCA testing in appropriate patients.

In spite of pre-clinical data demonstrating increased radiosensitivity for BRCA1/2-mutated BC cells lines, this large, previously unexamined dataset found BRCA1/2 mutations did not predict an improved OS or DFS for patients who received RT. When compared with WT BRCA patients, patients with BRCA1/2 mutations were found to have tumors of higher grade and clinical stage and to undergo more mastectomies. In a comparison with BRCA2-mutated patients, patients with mutations of BRCA1 were younger, more often ER/PR negative, and more likely to have high-stage tumors.

Our study identified 6 'HRD associated miRNAs' such as miR-106b, miR-93, miR-17, miR-20a, miR-200b, and miR-429 as novel miRNA-based signatures associated with HR deficiency in TNBC.

As a result, 56 patients were BRCA screened, and four referrals were made to receive genetic counseling. Education enhanced knowledge, increased screening tool use, and resulted in improvement in genetic referrals through the EHR.

P=N/A, N=109, Terminated, University Health Network, Toronto | Trial completion date: May 2022 --> May 2023 | Active, not recruiting --> Terminated; This study did not collect sufficient data for primary endpoint analysis.