Retesting of women who are negative for a and mutation using a 20-gene panel.

Background: The value of retesting women who previously tested negative for a pathogenic variant (mutation) in and using an expanded panel of breast and ovarian cancer genes is unclear.

Methods: We studied 110 -negative women who were retested using a panel of 20 breast and/or ovarian cancer susceptibility genes at the Advanced Molecular Diagnostics Laboratory (AMDL) at Mount Sinai Hospital in Toronto between March 2017 and March 2019. All patients had previously tested negative for pathogenic variants at the AMDL between January 2012 and March 2018 and were subsequently referred for retesting by their physician.

Results: Overall, six pathogenic variants in genes other than and were found (prevalence 5.5%). There were two pathogenic variants found in , and one found in each of , , and . The prevalence of pathogenic variants was 6.5% for women affected with cancer (6 of 93), including 4.9% for women with breast cancer (4 of 82) and 22.2% for women with ovarian cancer (2 of 9). None of the 17 unaffected women had a clinically significant or pathogenic variant. There were 44 women (40%) for whom the result of the panel test was inconclusive due to the detection of a variant of uncertain significance.

Conclusions: Our findings indicate that the retesting of /-negative individuals with an expanded panel of 20 breast and ovarian cancer genes can produce clinically relevant results, with a yield of 5.5% for pathogenic variants in genes other than and .