Patients with genetic mutations in BRCA1 or BRCA2 have 30-60% likelihood of developing a second primary breast cancer and between 11 and 45% risk of ovarian cancer, HER-2/neu is overexpressed in ~30% of human breast tumors and it has a predictive role in chemotherapy and endocrine therapy.
Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
The high incidence of ovarian cancer suggests that oophorectomy should be recommended in female BRCA1 and BRCA2 mutation carriers with a diagnosis of breast cancer, especially those with stage I disease.
The frequency of genomic rearrangements in BRCA1 was assessed in 42 American families with breast and ovarian cancer who were seeking genetic testing and who were subsequently found to be negative for BRCA1 and BRCA2 coding-region mutations.
The most significant risk factor for ovarian cancer is an inherited genetic mutation in one of two genes: breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2).
The major areas on which recent reports have focused include: (1) an expanded understanding of the BRCA1 and BRCA2 mutation spectrum and the frequencies of deleterious alleles in various ethnic groups; (2) investigations on how information is best transmitted to high-risk family members via genetic counseling; (3) an analysis of patient management changes based on genotype results; (4) social issues surrounding predictive testing for breast/ovarian cancer genes, including health insurance and discrimination concerns; and (5) an investigation into gynecologists' knowledge of ovarian cancer genetics, and their ability to provide genetic counseling for ovarian cancer to their patients.
The aim of the present study is to analyze the relationship of the incidence of mutations in the two major genes BRCA1 and BRCA2 conferring risk of breast cancer (BC) and ovarian cancer (OC) with the cancer burden in families and with the presence and age of onset of BC/OC.
Research on the utilization of genetic testing services for mutations in BRCA1 and BRCA2 has focused on women with a strong family history of breast and ovarian cancer.
These results suggest that both genetic and nongenetic factors modify cancer risks among BRCA1 and BRCA2 mutation carriers, and that genetic modifiers and other familial factors may influence risk specifically for either breast or ovarian cancer.
To address this gap, we sought to identify previously undescribed OVCA risk variants through the whole exome sequencing (WES) and candidate gene analysis of 48 women with ovarian cancer and selected for high risk of genetic inheritance, yet negative for any known pathogenic variants in either BRCA1 or BRCA2.
Women with a BRCA1 or BRCA2 mutation are at an elevated risk of developing breast and ovarian cancer; however, it is unclear to what extent family history influences the uptake of cancer prevention options.
The majority of inherited breast and ovarian cancer susceptibility is due to mutations in the BRCA1 and BRCA2 genes; however, other genes responsible for inherited susceptibility to these diseases are yet to be identified.