Approximately 5% of all breast cancers are due to one of the high-risk breast cancer genes BRCA1 and BRCA2, or possibly to a third or fourth moderate- to high-risk gene(s).
The imminent isolation of BRCA1 will make predictive testing for breast cancer a reality for many women and likely will pave the way for novel diagnostic and therapeutic strategies in the future.
Individuals who inherit a deleterious mutation in BRCA1 or BRCA2 are at very high risk for breast cancer but there are several strategies available for successfully managing this risk.
The N-terminus of nibrin (NBN) contains a tandem breast cancer 1 (BRCA1) carboxy-terminal (BRCT) domain that represents one of the major mediators of phosphorylation-dependent protein-protein interactions in processes related to cell cycle checkpoint and DNA repair functions.
A panel of ER<sup>+</sup> BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 <sup>wt</sup> or ESR1 <sup>Y537S</sup> , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780).
Overall, our data indicate that the p85 subunit is a valid target for therapeutic approaches and suggest that the structure of the peptide used in our study could be utilized for the development of novel drugs to apply in combination with therapies that fail to cure BCs with high PI3K activity.
These results indicate that the observed expression of Skp2B in breast cancer does contribute to tumorigenesis at least in part by modulating the activity of the estrogen receptor.
Because of the role of estrogens in promoting the growth and progression of breast cancer, there is great interest in exploring ways to functionally inactivate the ER, thereby suppressing ER-mediated gene expression and cell proliferation.
The breast cancer susceptibility gene BRCA2 is expressed in a wide range of tissues as an 11-kb mRNA transcript that encodes a 3418-amino acid protein involved in the response to DNA damage.
Finally, neurofibromin 1, synaptonemal complex protein 2 and tumor protein 53 were predicted to be involved in the interaction network of BRCA1 and BRCA2 in breast cancer and ovarian cancer.
The ability to isolate discrete epithelial subpopulations from mammary tissue has recently directed attention to luminal progenitor cells - the descendants of mammary stem cells - as the likely 'cells-of-origin' in BRCA1-associated breast cancer.
To determine if genetic factors predispose these patients to develop breast cancer, we evaluated breast cancer specimens for loss of heterozygosity (LOH) at regions where BRCA1 and BRCA2, two breast cancer tumor suppressor genes, are located.
In a large multiethnic case-control study, the G/A870 polymorphism conferred no significant risk for breast cancer overall or by stage or estrogen receptor (ER) status.