Variants of uncertain significance and contralateral risk-reducing mastectomy in early-stage breast cancer across safety-net and private hospital settings.

Abstract

10603 Background: Germline genetic testing informs surgical decisions in early-stage breast cancer. Guidelines recommend considering contralateral risk-reducing mastectomy (RRM) for patients with pathogenic or likely pathogenic variants in high-risk genes, but not for those with variants of uncertain significance (VUS). Despite this, VUS results may still affect surgical decisions. This study examines the impact of VUS on surgical decision-making across two university-affiliated settings: a safety-net hospital and a private hospital. Methods: We retrospectively reviewed patients with early-stage invasive breast cancer treated between 2012 and 2022 who underwent germline testing before surgery at both a safety-net and a private hospital. Patients with VUS were compared with genetically negative controls. Logistic regression was used to identify factors associated with RRM. Results: The cohort included 86 safety-net VUS patients, 115 safety-net controls, 102 private VUS patients, and 97 private controls. Table 1 highlights demographic differences between the hospitals. RRM was performed in 28 safety-net VUS patients (32.6%), 20 safety-net controls (17.4%), 37 private VUS patients (36.3%), and 45 private controls (46.4%). Stepwise regression analysis of the full cohort showed that treatment at the private hospital was independently associated with higher rates of RRM compared with the safety-net hospital, regardless of VUS status (OR 4.52, 95% CI 2.10 - 9.75, p < 0.001). Additional factors associated with higher RRM rates included higher tumor stage, higher tumor grade, and younger age at diagnosis. In hospital-specific analyses, VUS status did not influence RRM decisions at the private hospital. However, at the safety-net hospital, patients with VUS were more likely to undergo RRM than those with negative genetic testing (OR 2.38, 95% CI 1.09 - 5.21, p = 0.031). Conclusions: Surgical decision-making for RRM is influenced by multiple clinical and institutional factors. While VUS status did not affect surgical decisions at the private hospital, it was associated with increased RRM rates at the safety-net hospital. This finding suggests that differences in counseling practices and patient perceptions of genetic risk may exist within the safety-net setting, where patients may face more uncertainty about access to future care. Further studies are needed to better characterize these disparities and promote guideline-concordant care. Patient demographics by hospital. Safety-Net (n = 201) Private (n = 199) p-value Race/Ethnicity Non-Hispanic White 8 (4.0%) 116 (58.3%) < 0.001 Non-Hispanic Black 41 (20.4%) 39 (19.6%) Hispanic 141 (70.1%) 12 (6.0%) Other 11 (5.5%) 32 (16.1%) Language Spoken English 72 (35.8%) 199 (100%) < 0.001 Non-English 129 (64.2%) 0 (0%) Insurance Insured 62 (30.8%) 196 (98.5%) < 0.001 Uninsured 139 (69.2%) 3 (1.5%)