Use of breast surveillance between women with pathogenic variants and variants of uncertain significance in breast cancer susceptibility genes

Background: Use of surveillance mammography and magnetic resonance imaging (MRI) has been understudied among women with variant of uncertain significance (VUS) compared to pathogenic and likely pathogenic variants (P/LP). Methods: Using data from two cancer settings, we calculated use of risk-reducing mastectomy (RRM) and surveillance during each 13-month span after genetic testing up to 6 years afterwards for a cohort of genetically elevated risk women. Results: Of 889 women, VUS carriers were less likely to undergo RRM compared to those with P/LP (hazard ratio [HR], 0.17; p = <.001) and high-risk women were more likely to undergo RRM than average-risk women (HR, 3.91; p =.005). Longitudinally, surveillance use among unaffected women decreased from 49.8% in the first year to 31.2% in the sixth year after genetic testing. In comparison, a greater proportion of women with a personal history of breast cancer underwent surveillance, which increased from 59.3% in the first year to 63.6% in the sixth year after genetic testing. Mammography rates did not differ between women with P/LP and VUS within the first 13 months after genetic testing and up to 4 years afterward. Over the first 4 years after genetic testing, women with VUS were less likely to undergo annual MRIs compared to P/LP. Conclusion: The authors found that VUS, whether in high or moderate penetrance breast cancer susceptibility genes, was associated with lower use of annual breast MRI compared to P/LP variants and equivalent use of annual mammography. These results add important evidence regarding VUS-related breast surveillance.