BRCA mutation

P2, N=73, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Mar 2025 --> Jul 2026 | Trial primary completion date: Mar 2024 --> Jul 2024

In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as "continuous-metastasis type" with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.

Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.

This qualitative study revealed the key sources of information influencing attitudes regarding RRGS and how women consulted different sources of information to reach a decision. Results underscore the need for greater attention to women's information needs in the context of psychological readiness, particularly amidst the pandemic. Research involving a larger sample size may help to better inform how support can be provided to individuals with BRCA and LS mutations considering RRGS.

P1, N=0, Withdrawn, National Cancer Institute (NCI) | N=33 --> 0 | Suspended --> Withdrawn

The present study provides evidence, through lower GM volume, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, postsurgical ERT seems to ameliorate GM losses.

P1, N=48, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Mar 2024 --> Mar 2025

Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCAm, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.

Prophylactic measures encompass a range of interventions, including chemoprevention, hormonal inhibition, oophorectomy, and mastectomy. Despite their efficacy in mitigating breast cancer incidence, these interventions carry potential side effects and psychological implications, necessitating comprehensive counselling tailored to individual cases.

Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.

Normalizing both biomarkers emerged as the most effective predictive marker for the 1-year recurrence rate, regardless of BRCA mutational status. A negative HE4 value can be a useful predictor for 1-year recurrence-free survival in patients with BRCA mutations.

P1/2, N=14, Terminated, Avenge Bio, Inc | Trial completion date: Aug 2026 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Aug 2026 --> Apr 2024; Sponsor Decision to close study

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.

Crucially, it is becoming increasingly evident that cancer cells utilize error-prone polymerases to sustain ongoing replication in response to oncogenic mutations which inactivate key DNA replication and repair pathways, such as BRCA deficiency. This accelerates mutagenesis and confers chemoresistance, but also presents a dependency that can potentially be exploited by therapeutics.

Our findings underscore the possibility of distinct molecular mutation patterns in EAC among different races. Further studies are needed to validate our findings, which could contribute to precision medicine in EAC.

To advance the validation of miRNAs as clinically relevant biomarkers, additional investigations within larger and meticulously selected patient cohorts are deemed imperative. These microRNA entities hold the potential to emerge as groundbreaking and readily accessible tools, poised for seamless integration into the landscape of clinical practice.

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.

Weaker or no interaction was observed for these residues with PARP2 and PARP3. This approach advances our understanding of PARP-1 specific inhibitors and their mechanisms of action, facilitating the development of targeted therapeutics.

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.

Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition. The concept of "non-hereditary" familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

Our findings suggest that MCU alterations may be linked to BRCA progression, unveiling new diagnostic and prognostic implications for MCU in BRCA. The study underscores MCU's role in the tumor immune microenvironment and cell cycle progression, positioning it as a potential tool for BRCA precision medicine and drug screening.

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

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

Network meta-analysis results showed that cisplatin combined with nab-paclitaxel or paclitaxel was superior to docetaxel plus capecitabine in terms of PFS and ORR. For PD-L1 and BRCA mutation-positive tumors, atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option. Neutropenia, diarrhea, and fatigue are frequently occurring serious adverse events.

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.

Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

P3, N=1602, Recruiting, University Health Network, Toronto | N=1150 --> 1602

The unique BRCA mutational profile in the Chinese Han highlights the potential for standardized population-based BRCA variant screening to enhance BRCA mutation-related cancer prevention and treatment.

No abstract available

P1/2, N=17, Terminated, SK Life Science, Inc. | N=96 --> 17 | Trial completion date: Sep 2024 --> Mar 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Mar 2024; The study has been terminated based on portfolio prioritization. No safety trends or issues were identified at any dose level.

Treatment usually follows the same principles as FBCs (systemic therapy, surgical excision, and radiotherapy), with poorer prognosis to same treatment approach, possibly owing to its advanced stage at presentation. This is a rare entity which requires further research to ascertain need for different management approach than FBCs.

In conclusion, the evolving landscape of HER2-positive early-stage breast cancer treatment, characterized by targeted therapies and multidisciplinary approaches, underscores the need for ongoing research and collaborative efforts. The aim is to refine treatment strategies and enhance patient outcomes in this dynamic and rapidly evolving field.

Many are searching for reliable biomarkers of immune response to increase efficacy of ICI therapy involving ovarian cancer. In this review, we examine the evidence supporting the combination of PARPi and ICIs in ovarian cancer, which is still lacking.

Prophylactic mastectomy is a reliable strategy for significantly reducing the number of breast cancer incidence in high-risk patients regardless of the selected method of mastectomy. These operations allow for the subsequent reconstruction with the whole spectrum of reconstructive options.

(4) The individualized assessment of BRCA mutations is an important tool for the risk stratification of PCa patients. It is also a population screening tool which can guide our risk assessment strategies and achieve better results for our patients and their families.

CRS may not be a prognostic factor in patients with BRCA mutations and those receiving frontline maintenance therapy.

P2, N=11, Active, not recruiting, City of Hope Medical Center | Trial completion date: Mar 2024 --> Jun 2024 | Trial primary completion date: Mar 2024 --> Jun 2024

Primary cytoreductive surgery was associated with improved survival in women with stage III/IV BRCA mutated high grade serous ovarian cancers compared with neoadjuvant chemotherapy.

Although the related literature is often controversial, recently published case reports and/or randomized studies demonstrated the effectiveness of PARPi in treating patients with somatic BRCA mutations. The aim of this review is to summarize the predictive role of somatic BRCA mutations and to provide further assistance for clinicians with the identification of patients who could potentially benefit from PARPi.

We observed a significant increase in the use of systemic therapy among TNBCs, whereas carboplatin and dose-dense regimens showed the most prominent upsurge in the neoadjuvant setting. Moreover, the use of neoadjuvants was positively correlated with less invasive breast and lymph node surgeries. The presented data align with general trends observed in other countries and will contribute to expanding knowledge in the planning of treatment regimens and their outcomes.

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.