BRCA1 positive

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.

Furthermore, the downregulation of KLF5 expression promotes the DNA damage induced by olaparib and significantly reduces the IC 50 of the RARP inhibitor in pancreatic cancer cells...Our results indicate that inhibition of KLF5 may induce BRCAness in a larger pancreatic cancer subset with proficient BRCA. The combination of KLF5 inhibitors and PARP inhibitors provides a novel treatment strategy to enhance the sensitivity of BRCA1-proficient pancreatic cancer to PARP inhibitors.

Considering partial or focal BRCA1 methylation, caution has to be taken as this epigenetic alteration, which may progress to complete methylation status, was detected in non-neoplastic breast tissues adjacent to the cancerous ones and even normal breasts. This triggers application of extended screening programs, including BRCA1 methylation, for identification of women at risk, and can benefit from early intervention.

Recently, they have been shown to be responsive to treatment with poly ADP-ribose polymerase inhibitors, such as niraparib, olaparib, and rucaparib, used in combination with abiraterone acetate and prednisone or prednisolone, or as monotherapy...The top five treatment regimens for mCRPC were ADT monotherapy (19%), enzalutamide (ENZ; 14%), olaparib (OLA; 13%), abiraterone acetate (AA; 11%), and docetaxel (DOC; 10%), with 14% of patients receiving ≥1 medication... Among treated patients with BRCA+ mCRPC, ADT monotherapy, ENZ, OLA, AA, and DOC were most commonly used. The majority of ADT monotherapy patients died, while a substantial proportion of patients initiating 1L therapy died or initiated a clinical trial drug and did not advance to 2L, suggesting unmet need for more effective 1L treatment for patients with BRCA+ mCRPC.

Fifty percent of BRCA1/2 positive women in our study had not undergone annual imaging-based surveillance by mammography or MRI, and none had undergone annual dual screening with mammography and MRI, indicating inadequate breast cancer surveillance in this high-risk group.

PGT-M is a viable option for BRCA-positive patients to avoid transmission while building their families. Most patients in our cohort achieved pregnancy with BRCA-negative euploid embryos.

BRCA1/2-positive breast cancer with DCIS components is more likely to be hormone receptor-positive and of lower grade compared to patients with IDC only. A tailored approach might be necessary in establishing treatment options for breast cancer patients with BRCA1/2 mutations according to the presence of DCIS.

Although this study did not meet its primary endpoint, there were 2 TNBC patients without a gBRCA1/2 mutation who achieved a partial response to this non-chemotherapy regimen. Future biomarker testing may help elucidate these findings and possible predictors of response.

This study profiles HRD status in the Indian population. It underscores the fact that BRCA1/2 mutational analysis alone cannot capture HRD positivity. Importantly, using an expanded HR panel did not identify additional mutations as potential causes of the observed HRD.

Positive BRCA1 expression had proven to be associated with advanced stage & grade of tumors, as well as worsened prognostic survival parameters (metastasis, recurrence, residual disease, and mortality) in patients with ovarian serous carcinoma.

This Quality Initiative to improve testing and identification of HRR mutations in patients with mCRPC led to a 33% relative increase in HRR testing, demonstrating how QI programs can transform care and move the field toward individualized, precision medicine.

HR <1 (bold) favors NIRA+AAP treatment; Nominal p-value is from a non-stratified log-rank test. Conclusions Longer follow-up of the Asian subgroup confirms initial observations of a benefit from NIRA+AAP in BRCA+ mCRPC pts, which is consistent with the overall MAGNITUDE study results.

Lin's concordance correlation coefficient for the 24 samples simultaneously examined via both assays was 0.87, indicating a nearly perfect agreement. In conclusion, the addition of gLOH analysis could assist in the detection of additional patients eligible for treatment with PARPis.

The down-regulation of DNA repair signature in VLS was functionally validated by a lower % of RAD51 and BRCA1-positive tumor cells. If these data can be corroborated in a prospective trial, an easy, cost-effective test could be routinely used to better manage treatment in MPM patients.

Approximately one in ten patients with HR+/HER2-, and half of the patients with TNBC, meet the high-risk criteria according to OlympiA. Half of these patients do not meet the criteria for hereditary cancer testing and should therefore be tested for the presence of gBRCA1/2 mutations, irrespective of their own or family cancer history. The overall number of patients with early breast cancer benefiting from olaparib needs to be investigated in future studies.

Associations with poverty status, education, and healthcare discrimination outcomes were not statistically significant. Improving patient-provider interactions that can contribute to medical mistrust should become a priority for the care of high-risk US minority women with BRCA1/2 mutations.

This study provided significant information regarding rare variants observed in the Turkish population because it was carried out with a large patient group. Personalized treatment options and genetic counseling for the patients are therefore made facilitated.

A total of 23 differentially expressed miRNAs, 12 up-regulated and 11 down-regulated, were found in non-BRCA compared to BRCA cases. Among them, 12 miRNAs were also differentially expressed between non-BRCA cases and control group, thus representing a specific miRNA expression pattern of non-BRCA patients; ROC curves showed very good diagnostic accuracy (mean AUC 0.80; p-value<0.05), suggesting that this miRNA-panel could potentially be used as diagnostic/predictive signature in hereditary-familial non-BRCA BC/OC.ConclusionOverall, these results suggest that the analysis of circulating miRNAs expression levels, based on the BRCA1/2 germline mutational status, could provide important information for characterizing and putatively distinguishing familial-hereditary BC/OC cases, particularly non-BRCA group, and might be considered as potentially applicable in screening and prevention programs.

The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

In this systematic review we concluded that B vitamin supplements have varying data regarding safety and efficacy in cancer. Taking into account the etiology of the cancer, the specific B-vitamin, and the presence of any side effects could help guide utilization of the data found in this review. Large, randomized controlled trials are needed to confirm these findings among various cancer diagnoses and stages. Given the widespread utilization of supplements, healthcare providers should understand the safety and efficacy of vitamin B supplementation to address questions that arise in caring for those with cancer.

In the surveillance of BRCA mutation carriers, radiologists should be aware that the morphological differences between tumors are quite different between BRCA1 and BRCA2 patients.

In this study, we define the role of BRCA1/2 mutations as a significant risk factor in the development of BIA-ALCL in patients with BC reconstructed with textured implants. These results will help decision making for women with BRCA1/2 mutations undergoing breast reconstruction, or with textured implants in place. Analysis of pathogenic variants in other DNA repair genes in this cohort potentially affecting lymphomagenesis is ongoing.

This quality initiative to improve testing and identification of HRR mutations in patients with mCRPC led to a 33% relative increase in HRR testing. Quality initiative programs are critical to transforming cancer care and moving the field closer toward individualized, precision medicine.

P2, N=54, Completed, AstraZeneca | Active, not recruiting --> Completed

Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.

32 mutated, 19 negative and 15 were missed as they were unable to say or remember the result. Only 51 healthy males, with at least one female DRG mutated relative, were interested to be tested. This means that out of 378 men relatives of patients with DRG mutations, only 117 had already been tested or decided to do it with us, so 117/378 (31%) wanted to know whether they carried the mutation.

P3, N=216, Terminated, Tesaro, Inc. | Completed --> Terminated; The study was terminated due to futility.

For germline BRCA1-mutated breast cancer, TP53 R175H was unanimously the most frequent mutation among the three germline cohorts. Our study provides lists of potential shared neoantigens among BRCA1-related breast cancer, which may be used in developing off-the-shelf neoantigen-based vaccines.

Nivolumab plus rucaparib is active in patients with HRD-positive postchemotherapy or chemotherapy-naïve mCRPC, particularly those harboring BRCA1/2 mutations. Safety was as expected, with no new signals identified. Whether the addition of nivolumab incrementally improves outcomes versus rucaparib alone cannot be determined from this trial.

This study provides insight into how a sample of BRCA1/2-positive women both with and without cancer fare post-genetic counseling as compared to three normative female populations. Results infer the need for additional education, patient-provider training, and mental health referrals to support this population in order to circumvent unintended consequences and to improve psychosocial health in those being tested for, and those who test positive for, BRCA1/2 genetic mutations.

In silico analysis of target/pathway genes of the differentially expressed miRNAs revealed an enrichment of genes involved in different cancer types (e.g. prostate, lung, melanoma) and key biological processes, including cell cycle, apoptosis, focal adhesion and growth factor signaling pathways. Conclusion Overall, these preliminary results suggest that the analysis of the expression levels of circulating miRNAs in familial-hereditary BCs, based on the BRCA1/2 germline mutational status, could provide, once extended and confirmed on a larger number of patients, important information for characterizing and putatively distinguishing familial BRCA and non-BRCA BCs, and might be considered as potentially applicable in screening and prevention programs.

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.

Two subthemes also emerged within the first theme, which are termed "Pre-vivor," and "Testing Intuition." Participants indicated that genetic testing/counseling improvements would be helpful for women in this population surrounding quality care, including sensitivity training for healthcare professionals involved in testing/counseling, additional educational resources, and increased emotional and financial support. Although these recommendations may be beneficial, more widespread research with greater generalizability to disparate groups may be necessary prior to implementation.

On a theoretical level, our findings partially supported the Health Action Process Approach as a valuable model based on which interventions could be developed in the context of cascade screening for BRCA1/2 genetic testing. Those results supported the importance of integrated genetic counselling sessions with a strict collaboration between geneticists and psychologists together with interventions planned to increase men's self-monitoring ability to support their self-efficacy.

The safety run-in indicated that this combination is safe and well tolerated with mostly grade 1-2 AEs. This combination therapy has moved into the phase II trial, with 2 cohorts. Cohort A includes BRCA-wildtype patients with TNBC and cohort 2 includes those with a BRCA mutation and HER2-negative disease.

Furthermore, since much of the research on the lived experiences of BRCA1/2 has been on highly-educated, non-Hispanic white women, few studies have focused entirely on medically-underserved populations, which was the entirety of our sample. This work adds an important intersectional lens in which to better understand the experiences of living with a BRCA1/2 mutation.

Our study identifies disparities in genetic testing resources among women living in suburban and rural areas. These findings can be used to inform future care, research, and community resources that may impact services relating to genetic testing within these locales.

According to the existing literature evidence pregnancy after therapy for breast cancer in BRCA carriers is safe for the mother and offspring, but patients' needs, oncofertility counseling and fertility-sparing strategy should be carefully planned before starting the cytotoxic treatment.

To date, this is the first study to analyze anxiety and depression considering several COVID-19 predictors among BRCA1/2-positive women. Our findings can be used to inform future research and advise COVID-19-related mental health resources specific to these women.

A positive gBRCA1/2 mutation status is not a risk factor to acquire CH-associated gene mutations. OC patients may benefit from monitoring CH-associated gene mutations, especially following carboplatin exposure. Future clinical studies are required to assess whether treatment regimen should be adapted according to individual t-MN risks.

P2, N=54, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2021 --> Dec 2022

BRCA1 expression indicates a poor prognosis in resected NSCLC patients. BRCA1 might serve as an independent biomarker to predict clinical outcomes and help to customize optimal adjuvant chemotherapy for NSCLC patients who had received surgical therapy.