Here, we show that fork degradation is no longer detectable in BRCA1-deficient cancer cells exposed to multiple cisplatin doses, mimicking a clinical treatment regimen.
Therefore, using two large series of publicly available breast cancer datasets, namely that from The Cancer Genome Atlas and Wellcome Trust Institute, we sought to investigate the association between BRCA1- and BRCA2-deficiency with features of genomic instability, expression of PD-L1 and PD-1, landscape of inferred tumour-infiltrating immune cells, and T-cell inflamed signature in breast cancers.
The provision of genetic testing to high-risk women with a BRCA1 and two mutation probability of ≥ 10% based on the individual family cancer history appears to be a cost-effective option for the SHI.
A total of 128 patients diagnosed with FIGO stage III-IV high-grade serous ovarian cancer (HGSOC) between 2008 and 2017 and underwent BRCA1/2 gene testing at the time of or within two years from cancer diagnosis were included in this study.
Therapeutic strategies designed to tinker with cancer cell DNA damage response have led to the widespread use of PARP inhibitors for BRCA1/2-mutated cancers.
In this study, we performed targeted sequencing of BRCA1/2 in 145 breast cancer (BC) patients with a family history of BRCA-associated cancers and 47 age-matched cancer-free control individuals with or without a family history of cancer.
Moreover, MCL1 inhibition potentiates the in vivo efficacy of PARP inhibition (PARPi), underscoring the therapeutic potential of this combination for treatment of BRCA1-mutated cancer patients with poor response to PARPi monotherapy.
Data from the IMPACT study ( ClinicalTrials.gov NCT00261456) that the cancer detection rate is substantially elevated in BRCA1 and BRCA2 carriers at prostate specific antigen greater than 3 ng/ml has helped establish the importance of close prostate specific antigen screening in these men.
The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with BRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free.
If women are aware of their BRCA1/2 status, however, they can make timely decisions about preventive measures such as chemoprevention with hormonal agents or undergoing prophylactic surgery, all of which have been shown to reduce the risk of cancer and overall mortality.
Despite calls for BRCA1/2 population screening, there remains a critical need to identify those most at risk who should receive cancer genetics services.
The alleles XRCC1-Gln (OR 5.11; 95% CI 5.68-11.64, p < .0001), hMSH2-Asp (OR 4.66; 95% CI 3.90-5.56, p < .0001), XPD-Gln (OR 2.65; 95% CI 2.24-3.14, p < .0001) and BRCA1-L (OR 1.45; 95% CI 1.24-1.71, p < .0001) genes were strongly correlated with this malignancy.
Germline mutations of the genes BRCA1 and BRCA2, which encode proteins essential for the repair of double-strand DNA breaks through homologous recombination, lead to increased cancer predisposition.
IMPLICATIONS: The analysis of the current study on BRCA1 structural and functional defects on cancer risk and classification presented may improve clinical interpretation and therapeutic selection.
Here we show that in the 2.7% and 1.8% of patients with advanced-stage cancer and germline pathogenic or somatic loss-of-function alterations in BRCA1/2, respectively, selective pressure for biallelic inactivation, zygosity-dependent phenotype penetrance, and sensitivity to PARP inhibition were observed only in tumour types associated with increased heritable cancer risk in BRCA1/2 carriers (BRCA-associated cancer types).
A total of 54 (23.3%) ovarian cancer patients were found to harbor BRCA1/2 deleterious mutations, and BRCA1/2 mutations were significantly associated with Hereditary Breast and Ovarian Cancer-related tumors and family history of cancer.
Among the 481 female patients, 135 patients were detected to carry pathogenic (P)/likely pathogenic (LP) mutations (28.1%), which corresponded to 12 different cancer predisposition genes [14.6% (70/481) on BRCA1 gene, 5.0% (24/481) on BRCA2 gene, 8.5% (41/481) on non-BRCA1/2 genes].