Our study revealed a potential novel gene and multiple disruptive variants of BRCA2 for breast cancer risk, which may identify high-risk women in Chinese populations.This article is protected by copyright.All rights reserved.
For both BRCA1 and BRCA2 mutation carriers, none of the smoking-related variables was associated with BC risk, except smoking for more than five years before a first full-term pregnancy (FFTP) when compared to parous women who never smoked.
We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer.
Poly (ADP-ribose) polymerase (PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer therapies, especially in breast cancer gene (BRCA1 or BRCA2) mutation carriers.
This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations.
Eight PVs in ATM, BRCA2 (x2), PALB2, RAD51D, BRIP1, and MUTYH (x2) were identified in 7 of 44 individuals with breast cancer (15.9%, 95% CI: 7-30%), whereas none were identified in healthy controls (p = .01).
Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers.
Most data were available for DDR panels (n=12 studies), ataxia telangiectasia mutated (ATM; n=13), breast cancer susceptibility gene (BRCA)1 (n=14) and BRCA2 (n=20).
In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specific mortality rates, separately for BRCA1 and BRCA2 mutation carriers.
However, the pathogenic variants in BRCA1 and BRCA2 represent only a third of the causes of hereditary BC (Easton et al. in N Engl J Med 372:2243-2257, 2015).
Evaluation should be performed in a patient who has clinical signs or symptoms suggestive of ORS, especially in a premenopausal woman with breast cancer who is treated with an aromatase inhibitor following bilateral salpingo-oophorectomy (BSO), or a woman with a pathogenic variant in BRCA1 or BRCA2 who undergoes BSO for ovarian cancer risk reduction.
To the best of our knowledge, this report is the first to describe the highly pathogenic variant in the BRCA2 gene (rs483353122) and the likely damaging germline variant in the MUTYH gene (rs35352891) in Russian Mongoloid BC patients with young-onset and/or bilateral and/or familial BC.
Of 1054 BRCA-negative, high-risk Hispanic women, 4.5% carried a PV in a cancer susceptibility gene, increasing understanding of hereditary BC in this population.