Utilization of Cancer Screening, Prevention, and Treatment in Women With Variants of Uncertain Significance in Breast Cancer Susceptibility Genes.

Background: The presence of variants of uncertain significance (VUS) should not influence clinical management; however, prior studies on breast cancer-related health care utilization in women with VUS versus negative germline genetic test results have shown conflicting findings. This study evaluated whether receipt of a VUS influences breast cancer-related health care utilization.

Methods: This large study analyzed health care utilization and costs in women who underwent clinical multigene panel testing (MGPT) between 2015 and 2023 at a single commercial laboratory with ≥2 years of health insurance claims data available. Multivariable logistic regression was used to assess differences in the uptake of surgical, therapeutic, risk-reducing, and surveillance modalities, as well as the associated health care costs, between women with VUS or negative MGPT results after the return of test findings.

Results: Of 50,657 eligible women (mean age, 47.7 years), most were White (66.8%), had a family history of cancer (87.0%), and had commercial insurance (71.1%). Among 22,699 patients with breast cancer, those with VUS showed no differences from those with negative results in the uptake of surgical, therapeutic, risk-reducing, and surveillance procedures or in the adjusted cost of surgical procedures after genetic testing. Among 27,958 cancer-free women, those with negative results had modestly lower mammography use (odds ratio, 0.9; 95% CI, 0.8-0.9) compared with those with VUS. Breast cancer screening and treatment costs were no higher for women with VUS versus negative results, but were up to 10 times higher for those with positive results.

Conclusions: In a large, real-world sample of women with breast cancer and without any cancer, use of cancer treatments, surveillance, and risk-reducing measures did not differ between patients with VUS versus negative results, except for modestly higher mammography use. These findings offer reassurance that VUS results do not lead to overutilization or increased cost of health care.