BRCA1 mutation + BRCA2 mutation

The prevalence and spectrum of BRCAm in OC patients from Yunnan Province are different from those in other groups. BRCA status testing is advised for all OC patients, particularly those with a family history of HBOC.

In the case of the strong implication of BRCA PV/LPV with a negative result with one genetic test, different platforms could be considered in limited cases. Careful interpretation and further studies for the cross-validation of gene analysis platforms are needed.

Our study emphasizes the importance of tumor cell-derived DNA methylation in BC, reporting a different methylation profile between patients carrying mutations in BRCA1, BRCA2, and wild-type controls. Our minimally invasive approach could allow early cancer diagnosis, assessment of minimal residual disease, and monitoring of response to therapy.

This comprehensive analysis emphasizes the critical roles of BRCA1, BRCA2, TP53, and PMS2 in prostate cancer pathogenesis and highlights the importance of population-specific genetic screening.

The addition of whole-breast ultrasound to mammography and MRI screening in BRCA PSV carriers aged 30-39 years offered limited incremental benefit. MRI with 6 months supplemental mammography without US detected all cancer cases.

Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.

Although the literature does not conclusively establish a direct link between obesity and/or diabetes and the development of ovarian cancer, the indirect association highlights the need for further clinical studies. A general research gap related to risk factors of ovarian cancer could be observed in the South American region.

P1, N=52, Terminated, Nerviano Medical Sciences | N=150 --> 52 | Trial completion date: Dec 2024 --> May 2024 | Active, not recruiting --> Terminated; The study closure is related to sponsor decision to shift towards the clinical development of NMS-03305293 in combination in a broader range of indication and not based on emerging safety or efficacy concerns.

Our data supports considering ascitic cytology samples suitable for HRD testing and BRCA1 and BRCA2 mutation analysis. Further studies are needed to validate the practice of using ascitic cytology as a diagnostic specimen for HRD testing when tissue is not accessible, as it could prove crucial to provide ovarian cancer patients with essential information in an early stage of the diagnostic process.

These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .

In women with newly diagnosed breast cancer and prior to treatment, LV-GLS was worse in BRCA1 and BRCA2 mutation carriers compared to those with BRCA wildtype. These findings suggest that BRCA mutations may be associated with subtle changes in cardiac function. Whether differences in GLS translate to increased cardiovascular risk in women with BRCA mutations needs to be further characterized.

It specifically highlights genes associated with antigen processing and presentation, such as HLA-B, HLA-A and HLA-DRB1 and their possible effects on tumour progression and immune evasion. In summary, by utilizing machine learning approaches, we have the potential to aid in the development of precision medicine approaches for early detection and personalized treatment strategies.

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.