Impact of germline mutations on surgical decision-making in women with DCIS.

Abstract

10576 Background: Ductal carcinoma in situ (DCIS) is both a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have a low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for breast cancer recurrence. Uptake of genetic testing and treatment with risk-reducing surgeries (RRS), including bilateral mastectomy (BM), in women with DCIS, has not been well-studied. The aim of this study was to determine the prevalence of PVs in women with DCIS and the impact on surgical decision making. Methods: All women diagnosed with unilateral DCIS 2001-2020 enrolled in the Clinical Breast Care Project were identified. Demographic, genetic test results and surgical procedures were extracted from the database. Test-eligibility was assigned using National Comprehensive Cancer Network (NCCN) criteria. Panel genetic testing was performed in the research setting using DNA from 465 women. Statistical analyses were performed using Fisher’s exact tests and Chi-square analyses with p < 0.05 defining significance. Results: The overall PV frequency in women with DCIS was 8.1%. Within the test-eligible group, 35.1% pursued clinical genetic testing, including 13.2% who pursued testing only after a second cancer event. Of the 39 women with PV, 20 (51.3%) were detected only in the research setting, with 11 (28.2%) of these women not eligible for genetic testing based on NCCN criteria. In the 419 women who did not undergo BM at diagnosis, recurrence was significantly higher (p = 0.001) in women with PV (33.3%) compared to those without PV (11.6%). Conclusions: Genetic testing is suboptimal in women with a primary diagnosis of DCIS. Twenty percent of women with PV, who may have benefited from BM, did not undergo genetic testing at the time of diagnosis and recurred. These data suggest that genetic testing at the time of diagnosis should be standard for all women with DCIS.