Building the What Comes Next Cohort for BRCA1 and BRCA2 testing: a descriptive analysis

Area of Science:

• Genetics
• Oncology
• Public Health

Background:

• Understanding of BRCA1/BRCA2 gene mutations and cancer risk often relies on specialized clinic data.
• A generalizable cohort is needed to study healthcare utilization and outcomes post-genetic testing.

Purpose of the Study:

• To establish the "What Comes Next Cohort" of women undergoing BRCA1/BRCA2 testing.
• To enable the study of health care utilization and outcomes after genetic testing, irrespective of results.
• To assess the generalizability of BRCA1/BRCA2 testing criteria and yields.

Main Methods:

• Descriptive study of 15,986 adult women undergoing BRCA1/BRCA2 testing in Ontario, Canada (2007-2016).
• Data collected via chart review (demographics, family history, testing indications) linked to administrative health databases.
• Follow-up until September 2019 to evaluate cohort characteristics, testing indications, and results.

Main Results:

• 15,986 women tested; 2033 had positive results, 1175 variants of uncertain significance, 12,778 negative.
• Positive yields varied: 41.0% for predictive, 10.4% for Ashkenazi Jewish founder testing, 7.4% for complete gene analysis.
• Six provincial criteria had <10% positive yield; 3.0% of women negative for founder mutations tested positive for alternate variants.

Conclusions:

• Several BRCA1/BRCA2 testing criteria demonstrate low positive yields.
• The "What Comes Next Cohort" is crucial for studying the long-term implications of genetic testing, especially for women with negative results or uncertain significance variants.