Abstract PS8-08: Impact of genetic testing for hereditary breast cancer on screening and risk-reducing surgeries among multi-ethnic breast cancer survivors
Authors: Ro Vicky , Jones Tarsha , Trivedi Meghna S , McGuinness Julia E , Silverman Thomas , Chung Wendy K , Kukafka Rita , Crew Katherine D 
Published: February 2021

Introduction Current guidelines for cancer risk management for hereditary breast cancer focus on individuals with pathogenic/likely pathogenic variants (P/LP) in high penetrance genes. There is little consensus on prophylactic mastectomy for low/moderate penetrance genes or variants of uncertain significance (VUS). Furthermore, many guidelines for enhanced breast cancer screening are targeted to unaffected carriers, but not breast cancer survivors. Given the increasing use of multigene panel testing, more patients are receiving results of P/LP in low/moderate penetrance genes or VUSs. We aimed to investigate how multigene panel results impacted surgical and screening decisions among breast cancer patients. Methods We conducted a retrospective analysis of women diagnosed with stage 0-III breast cancer at Columbia University Irving Medical Center in 2013 or later, who received germline genetic testing. Clinical data were extracted from the electronic health record (EHR), tumor registry, and genetic testing portals. Patients were excluded if they had stage IV disease at diagnosis, had bilateral mastectomy before 2013, or had missing genetic test results or surgical reports. For the screening analysis, patients were excluded if they had bilateral mastectomy or did not have breast imaging in the EHR. Surgery type was defined by the most advanced breast surgery received. Enhanced screening was defined as use of breast ultrasound or MRI in the absence of breast symptoms and in the setting of a normal mammogram. Univariable and multivariable analyses were performed to assess the association between clinical factors and receipt of bilateral mastectomy or enhanced screening. Results Among 715 evaluable women, about two-thirds were 50 years or younger, with 45% white, 12% black, 27% Hispanic, 11% Asian, and 4% other. Most patients (69.5%) had benign/likely benign (B/LB) genetic test results, while 91 (12.7%) had P/LP and 127 (17.8%) had VUS. VUS rates were higher among racial/ethnic minorities (27% Asian, 25% Hispanic, 19% black) compared to white women (10%). About 31% of women underwent bilateral mastectomy, 25% unilateral mastectomy, and 45% lumpectomy. Bilateral mastectomy rates among patients with P/LP variants were higher compared to those with VUS or B/LB results (66% vs. 27% vs. 26%), particularly P/LP in high-penetrance genes (76%) compared to other genes (45%). On multivariable analysis, compared to patients with B/LB genetic results, P/LP was significantly associated with bilateral mastectomy (odds ratio [OR]=5.72, 95% confidence interval [CI]=3.43-9.53). Younger age at diagnosis and family history of breast cancer were also associated with bilateral mastectomy. Among patients with breast cancer screening data, almost half (43%) received enhanced screening (59% ultrasound, 25% MRI, 16% both). On multivariable analysis, patients with P/LP variants and age of diagnosis under 50 were more likely to receive enhanced screening (OR=4.43, 95% CI=1.59-12.33 and OR=1.92, 95% CI=1.09-3.38, respectively). Hispanic women compared to non-Hispanic whites and those with Medicaid rather than private health insurance were less likely to undergo enhanced screening. Conclusions We demonstrated that detection of P/LP variants on multigene panel testing influences surgical and screening decisions among breast cancer patients. Patients with VUS, a group enriched for racial/ethnic minorities, appropriately have similar surgical and screening decisions as those with B/LB results. Our findings suggest adequate genetic counseling and communication of cancer risk to multi-ethnic breast cancer survivors.

Citation Format: Vicky Ro, Tarsha Jones, Meghna S Trivedi, Julia E McGuinness, Thomas Silverman, Wendy K Chung, Rita Kukafka, Katherine D Crew. Impact of genetic testing for hereditary breast cancer on screening and risk-reducing surgeries among multi-ethnic breast cancer survivors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS8-08.