From the Journals

Breast cancer: More pathogenic variants detected as multiple-gene sequencing takes over


Key clinical point: For breast cancer patients in community practice, multiple-gene sequencing has rapidly replaced BRCA1/2-only testing, increasing detection of pathogenic variants with no associated increase in prophylactic mastectomy.

Major finding: The rate of pathogenic variant detection was substantially increased with multiple-gene sequencing versus BRCA1/2 only testing for higher-risk patients (12% versus 7.8%) and average risk patients (4.2% versus 2.2%).

Study details: A population-based retrospective cohort study of 5,026 patients with breast cancer diagnosed from January 2013 to December 2015.

Disclosures: Stanford University received research funding from Myriad Genetics for an unrelated project. No other conflicts of interest were reported.

Source: Kurian AW et al. JAMA Oncol. 2018 May 10. doi: 10.1001/jamaoncol.2018.0644.



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.

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