Management impact of preoperative germline genetic testing in patients with breast cancer at the Lifespan Cancer Institute.

Abstract

10523 Background: Breast cancer is a heterogenous disease and management is complex. Advances in next generation sequencing has allowed genetic testing to be more accessible. However, conveying results to patients and care team can be challenging due to various variant classifications. Diagnostic results have the potential to guide management. Nondiagnostic results can be misinterpreted. The extent to which preoperative genetic testing affects management of newly diagnosed breast cancer is unknown. Methods: Newly diagnosed breast cancer patients were identified via review of breast tumor board between May 2019 and March 2019 followed by chart review to collect detailed information. Results: 408 newly diagnosed breast cancer cases were queried. Genetic evaluation was recommended and completed in 68%, not recommended (did not meet NCCN criteria) in 30% and declined in 2.7%. The genetic evaluation recommended cohort was associated with a higher mastectomy rate in comparison with when not recommended (31% vs. 9%, p=0.0001). Of those who completed genetic testing: 12% harbored a pathogenic/likely pathogenic variant (PV/LPV), 26% had a nondiagnostic variant of uncertain significance (VUS) and 61% had negative testing. Comparison between nondiagnostic test results (negative and VUS) and diagnostic test results revealed significantly increased number of women in the diagnostic group who chose mastectomy over breast conservation therapy (BCT, nondiagnostic 20% vs diagnostic 39%, p=0.018). When negative, VUS, and PV/LPV were each independently analyzed, diagnostic test results again revealed a significantly increased number of mastectomies over BCT (p<0.05). Comparison of surgical choices in nondiagnostic VUS vs. negative results was not significantly different (Table). Comparing the surgical timelines, completing a genetic evaluation did not affect surgery timing (mean 2.3 vs. 2.2 months, p>0.5). Conclusions: Germline genetic testing in patients with newly diagnosed breast cancer impacts clinical management. Those harboring a diagnostic result were more likely to choose mastectomy over BCT. Not surprisingly, mastectomy rate was higher among those where genetic evaluation was recommended, possibly due to concerning personal or family history. The mastectomy rate was higher among those with a diagnostic result, indicating an understanding of the genetic testing significance by patients and the care team. More importantly, those who harbored nondiagnostic VUS did not make significantly different surgical choices compared with negative genetic testing, highlighting the critical role of proper genetic counseling and being part of the care team. We conclude consideration of genetic evaluation is clinically useful and feasible without affecting the surgical timeline.[Table: see text]