Rabbit Anti-Human BRCA1 (Phospho-Ser1524) polyclonal antibody

Purpose This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes. Materials and Methods We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment. Results The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with Inter- national Federation of Gynecology and Obstetrics stage different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135). Conclusion BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.

Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative forBRCA1orBRCA2pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result forBRCA1/2pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, includingATM,CHEK2,PALB2,PTEN,TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform a most comprehensive genetic analysis in these subjects, regardless the criteria concerning personal and family history of cancer established by the current guidelines. Our study revealed that the use of a NGS-based multiple-gene panel testing could increase the detection rates of germline alterations in bilateral breast cancer patients. Patients with unilateral breast cancer (UBC) have an increased risk of developing bilateral breast cancer (BBC). The annual risk of contralateral BC is about 0.5%, but increases by up to 3% inBRCA1orBRCA2 pathogenic variant(PV) carriers. Our study was aimed to evaluate whether all BBC patients should be offered multi-gene panel testing, regardless their cancer family history and age at diagnosis. We retrospectively collected all clinical information of 139 BBC patients genetically tested for germline PVs in different cancer susceptibility genes by NGS-based multi-gene panel testing. Our investigation revealed that 52 (37.4%) out of 139 BBC patients harbored germline PVs in high- and intermediate-penetrance breast cancer (BC) susceptibility genes includingBRCA1,BRCA2,PTEN,PALB2,CHEK2,ATM,RAD51C. Nineteen out of 53 positively tested patients harbored a PV in a known BC susceptibility gene (no-BRCA). Interestingly, in the absence of an analysis performed via multi-gene panel, a significant proportion (14.4%) of PVs would have been lost. Therefore, offering a NGS-based multi-gene panel testing to all BBC patients may significantly increase the detection rates of germline PVs in other cancer susceptibility genes beyondBRCA1/2, avoiding underestimation of the number of individuals affected by a hereditary tumor syndrome.