Abstract
Currently, genetic testing is offered only to women diagnosed with breast cancer who meet a defined set of criteria and is not included as standard-of-care treatment at the time of diagnosis. Thus, a significant number of women diagnosed with breast cancer may miss the opportunity for precision medical treatment and risk management. The effects of eligibility, timing, and uptake of genetic testing were evaluated in a cohort of women with invasive breast cancer diagnosed between 2001–2018. Risk status was estimated using NCCN BRCA1/2 testing criteria and panel testing was performed for all women who had genomic DNA available. Of the 1231 women, 57.8% were eligible for genetic testing. Uptake of testing within high-risk women was 42.7% of which 6.6% pursued clinical testing only after a second tumor event. Mutation frequencies were 15.8%, 5.5%, and 4.0% in high-risk women with clinical testing, high-risk women without clinical testing, and low-risk women, respectively. More than 4% of all patients harbored pathogenic or likely pathogenic mutations detected only in the research setting. Inclusion of panel testing at the time of diagnosis would allow for appropriate surveillance and treatment strategies to be employed to reduce the risk of secondary tumors and improve patient outcome.
Highlights
Discovery of the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes [1,2] led to the development of genetic tests to identify individuals at risk for hereditary breast and ovarian cancer (HBOC)
For patients with germline mutations in ATM, CHEK2, NBN, NF1, and PALB2, enhanced surveillance through addition of MRI may be warranted while breast cancer patients with mutations in BRIP1 or mismatch repair genes may benefit from risk-reducing salpingo-oophorectomy (RRSO), endoscopy, or colonoscopy
2.2017 criteria to a cohort of 1371 newly diagnosed breast cancer patients from Norway who were tested for BRCA1 and BRCA2 mutations, revealed that 32 of 38 (88.9%) mutation carriers would have been classified as high-risk [13]
Summary
Discovery of the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes [1,2] led to the development of genetic tests to identify individuals at risk for hereditary breast and ovarian cancer (HBOC). Two decades after the BRCA genes were identified, technical advances in generation sequencing allowed for the simultaneous assessment of multiple genes, decreasing cost and time to return of test results. Myriad Genetics’ patent on the BRCA1 and BRCA2 genes, which allowed for the development of multi-gene cancer predisposition panels that today are offered by multiple commercial companies [3]. As technologies to identify mutations in cancer predisposition genes have evolved, the utility for identifying patients with hereditary cancers has expanded from personal or family risk assessment to Cancers 2020, 12, 234; doi:10.3390/cancers12010234 www.mdpi.com/journal/cancers. For patients with germline mutations in ATM, CHEK2, NBN, NF1, and PALB2, enhanced surveillance through addition of MRI may be warranted while breast cancer patients with mutations in BRIP1 or mismatch repair genes may benefit from risk-reducing salpingo-oophorectomy (RRSO), endoscopy, or colonoscopy
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