Prophylactic mastectomy was most strongly associated with detection of pathogenic BRCA1/2 variants, according to Dr. Kurian and her coinvestigators. More women with those variants strongly considered the procedure and had it recommended by their surgeons, and ultimately, significantly more underwent the procedure (79.0% versus 37.6% for other pathogenic variants; P less than .001).
While those mastectomy outcomes were reassuring, Dr. Kurian and her colleagues said, their research uncovered two “important limitations” to multiple-gene sequencing that should be addressed.
They found that testing was done post surgically in 32.5% of women who had multiple-gene sequencing, compared with 19.9% of women who had BRCA1/2-only testing. Postsurgical testing is “too late” and limits its use to make decisions about surgical prevention of second cancers, they said.
They also found racial disparities in detection of variants of unknown significance (VUS). In particular, VUS were detected in 23.7% of white patients, compared with 44.5% of black patients and 50.9% of Asian patients. That’s because most of the genes were first sequenced in white patients, the investigators noted.