To the Editor: I read with interest the recent NCCN Guidelines Insights for Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015, in the journal.1 The NCCN Guidelines Insights offer clear evidence-based recommendations regarding how to address identified germline mutations associated with common and uncommon inherited cancer syndromes, the unclear role for multigene testing, and even guidance for patients who have germline variants of uncertain significance.2
However, how does one approach the patient who has a high pretest probability of having a germline mutation whose multigene test results show no mutations? For example, I recently saw a patient who, by age 57, had experienced 2 breast cancers and pancreatic cancer. Her sister had ovarian cancer at a young age. Next-generation sequencing (NGS) for 48 genes revealed no abnormalities associated with increased cancer risk.
The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version, 2.2016, suggest “individualized recommendations according to personal and family history” (page BRCA-2).2 The footnote mentions testing another family member. Is that based on data showing that patients with a high pretest probability have a significance false-negative testing rate with multigene testing? Are there studies showing that patients with negative multigene test results but who have a high pretest probability are at higher risk for cancers associated with common germline mutations compared with the general population?
With so many potential recommendations involved, citing the evidence for what to do for the patient with negative germline testing results is important as well.
Call for Correspondence
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References
- 1.↑
Daly MB, Pilarski R, Axibund JE et al.. NCCN Guidelines Insights for Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2105. J Natl Compr Canc Netw 2016;14:153–162.
