Should We Be Testing Beyond BRCA1/2 in Women of Ashkenazi Jewish Heritage with Breast Cancer?
BACKGROUND AND PURPOSE:
In the Ashkenazi Jewish population, there are 3 ancient founder mutations that occur with high frequency
BRCA1: 185delAG and 5382insC
There is limited data beyond these 3 founder mutations
Walsh et al. (JAMA Oncology 2017) sought to determine the frequency of cancer-predisposing mutations other than the BRCA1 and BRCA2 founder alleles among Ashkenazi Jewish with breast cancer
Prospective cohort study
Data derived from the New York Breast Cancer Study (NYBCS)
First diagnosis of invasive breast cancer
All 4 grandparents identified as Ashkenazi Jewish
DNA testing at the time of the original study focused on the 3 founder mutations
Current study sequenced 23 known candidate breast cancer genes
1007 probands were included in the study, 903 of which had no founder mutations
0.8% of these probands carried another pathogenic mutation in BRCA1 or BRCA2
3.4% of these probands carried a pathogenic mutation in another breast cancer gene
29 in CHEK2
Overall, there were 142/1007 (14.1%) women who had a significant germline mutation in the overall cohort and of those
73.8% were due to a BRCA1 or BRCA2 founder mutation
4.9% were due to another BRCA1 or BRCA2 mutation
21.8% of mutations occurred in a non-BRCA gene
Of women with BRCA1 or BRCA2 mutations, 51.4% had a mother or sister with breast/ovarian cancer history while the remainder did not have family history
Based on the above data, in women with of Ashkenazi Jewish background who have breast cancer, approximately 50% of women with pathogenic causative variants did not have a family history of breast cancer
Current guidelines recommend that a woman with breast cancer and of Ashkenazi Jewish heritage should have genetic testing
Due to the finding of a significant number of pathogenic mutations beyond the founder mutations, the authors recommend that in this cohort, breast cancer genetic testing should include a larger panel of genes and not be limited to BRCA genes
In addition, preventative options are now available, and the authors state
To discover a mutation only after cancer is diagnosed is a missed opportunity to have prevented that cancer. Many of these cancers could be prevented by offering genetic testing as described here to all women before they develop breast cancer, as part of routine medical care.
OBG Project CME requires a modern web browser (Internet Explorer 10+, Mozilla Firefox, Apple Safari, Google Chrome, Microsoft Edge). Certain educational activities may require additional software to view multimedia, presentation, or printable versions of their content. These activities will be marked as such and will provide links to the required software. That software may be: Adobe Flash, Apple QuickTime, Adobe Acrobat, Microsoft PowerPoint, Windows Media Player, or Real Networks Real One Player.
Disclosure of Unlabeled Use
This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of the planners. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.
Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information
presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
Jointly provided by
NOT ENOUGH CME HOURS
It appears you don't have enough CME Hours to take this Post-Test. Feel free to buy additional CME hours or upgrade your current CME subscription plan