BRCA1 mutation

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.

P1/2, N=51, Recruiting, Advanced Accelerator Applications | N=86 --> 51 | Trial completion date: Oct 2025 --> Dec 2026

To evaluate the efficacy and safety of biomarker-driven combinatorial therapies of pamiparib, tislelizumab, bevacizumab, and nab-paclitaxel in platinum-resistant, recurrent ovarian cancer. Recruitment is estimated to be completed by 2024 and results may be published by 2027. ClinicalTrials.gov: NCT05044871.

By cell viability assay, we found that PTIP-depleted and UFL1-depleted BRCA1 knockdown cells are less sensitive to PARP inhibitors than the siRNA targeting negative control BRCA1-deficient cells. These results identify a new mechanism by which PTIP UFMylation confers chemoresistance in BRCA1-deficient cells.

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.

DNA damage and cellular responses to DNA damage can be both the result and the cause of obesity and can strongly influence the development and treatment of obesity-associated diseases.

Germline BRCA mutations were associated with a higher frequency of G2/3 anemia in ovarian cancer patients who underwent first-line platinum-based chemotherapy. Moreover, the BRCA1 mutation appeared to be more strongly associated with the incidence of chemotherapy-induced anemia. Our findings warrant further investigation in larger, prospective studies to confirm these current findings and determine whether preventive interventions may be necessary.

Since many patients now can look forward to longer survival it is paramount to take care of the side-effects of the treatments, where focus is on cardiovascular disease and bone health management. Precision medicine has started also in prostate cancer; testing of BRCA1/2 mutation is mandatory for treatment with PARP inhibitors.

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

P1, N=30, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Apr 2024

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

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

Many private and public healthcare funders do not cover risk reducing surgeries, even when recommended as part of a risk reduction management plan for BRCA gene mutation carriers. Here, positions on these matters from different high income countries are discussed, stressing the importance of a common supranational or international regulatory framework to reach a trade-off between the economic interests of insurers and the rights of carriers not to disclose extremely sensitive information.

We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours.

Patients with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12 mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 ,d1, q3w or nab-paclitaxel 125 mg/m2, d1 and d8, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and encouraging antitumor activity for patients with clinical stage II/III TNBC. Chongqing Talents Project, Chongqing Key Project of Technology Innovation and Application Development and Chongqing Outstanding Youth Natural Science Foundation.

This comprehensive analysis of somatic mutations in HGSOC provides insight into potential therapeutic targets and molecular pathways for targeted interventions. AP3S1 was identified as being a key player in tumor immunity and prognosis, thus providing new perspectives for personalized treatment strategies. The findings of this study contribute to the understanding of HGSOC pathogenesis and provide a foundation for improved outcomes in patients with this aggressive disease.

The primary end point is an investigator-assessed objective response rate in each cohort. Clinical Trial Registration: jRCT2011200023 (ClinicalTrials.gov).

However, optimal identification of high-risk patients who may derive benefit from this genomically-directed therapy is debated. In this study, we sought to characterize the real-world proportion of gBRCA1/2 PV carriers eligible for adjuvant olaparib according to the OlympiA criteria, and to compare clinicopathologic characteristics and outcomes between eligible and ineligible patients.

P=N/A, N=69, Completed, Technical University of Munich | Active, not recruiting --> Completed

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

P2, N=298, Active, not recruiting, AstraZeneca | Trial completion date: Jun 2023 --> Dec 2024

The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

P1/2, N=116, Recruiting, Cantargia AB | Phase classification: P1b/2 --> P1/2

KRT14-positive cells are also more abundant with DNA damage than KRT14-negative cells. The obtained results indicate comprehensive cellular changes upon PALB2 mutations, even in the presence of half dosage of wild type PALB2 and demonstrate how PALB2 mutations may predispose their carriers to malignancy.

Immortalized ovarian cells derived from patients with germline BRCA1 or BRCA2 mutations showed substantially higher MMP1 expression than normal ovarian cells. However, the findings need to be validated in the future.

In this secondary analysis of the PAOLA-1 randomized clinical trial, patients with a BRCA-like tumor, but not those with a non-BRCA-like tumor, had a significantly longer survival after olaparib plus bevacizumab treatment than placebo plus bevacizumab treatment. Thus, the BRCA1-like classifier could be used as a biomarker for olaparib plus bevacizumab as a maintenance treatment.

Our experience reports optimistic the ADM covering the TE is seen successfully integrating during tissue expansion and becoming a vascularised new self-tissue. Complications rates are low and such ADM-assisted two-stage pre-pectoral reconstructive technique is a safe, practical, and reproducible method.

P=N/A, N=69, Active, not recruiting, Technical University of Munich | Trial completion date: Dec 2023 --> Apr 2024

P=N/A, N=600, Recruiting, Technical University of Munich | Trial primary completion date: Mar 2024 --> Mar 2025

The observed response rate and safety of SG are consistent with the results of the ASCENT trial, with efficacy observed in patients with brain metastases, but observed PFS and OS are numerically shorter.

Remarkably, Polθi binding to the Polθ-pol:DNA/DNA closed complex traps the polymerase on DNA for more than forty minutes which elucidates the inhibitory mechanism of action. These data reveal a unique small-molecule DNA polymerase:DNA trapping mechanism that induces synthetic lethality in HR-deficient cells and potentiates the activity of PARPi.

P2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

Olaparib is not a cost-effective maintenance treatment option. Companion diagnostics are an equally important cost driver as the drug itself.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

Due to the complexity of genetic divergence, inputs from each individual ancestry seem to carry independent contributions that interplay in the development of these complex disease phenotypes. By understanding these unique population characteristics, genomic ancestries hold a promising avenue for tailoring prognostic assessments and optimizing responses to oncological interventions.

Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.

P2, N=44, Recruiting, SWOG Cancer Research Network | Trial primary completion date: Jul 2025 --> Jul 2026

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

We present the case of a transgender woman with a family history of breast cancer and BRCA1 mutation and the therapeutic decisions made in a multidisciplinary team. Following this case, we review and discuss the published literature.

BC patients with PVs in BRCA1/2 have higher RS results that stem from distinct gene expression profiles in the majority of genes in the 21-gene assay.

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.