Healthcare utilization among individuals diagnosed with hereditary breast-ovarian cancer syndrome through a universal germline genetic testing program.
Authors: Gray Stacy W. , Hampel Heather , Solomon Ilana , Garcia Michael , Luong Marilan , Labib Sarah , Bonner Joseph D. , Shaktah Lawrence , Hong Christine , Idos Gregory , Lindsey Sidney S. , McDonnell Kevin , Park Wai , Roth Katherine G. , Sobotka Elise , Xiao Yi , Zukin Elyssa , Hamilton Stanley R. , Gruber Stephen B. 
Published: June 2023

10604

Background: Most individuals with Hereditary Breast-Ovarian Cancer Syndrome (HBOC) are unaware of their risk. Criteria-based testing will not close this gap as it fails to identify ~50% of mutation carriers. Universal germline testing (GT) in oncology stands to identify more mutation carriers and advance cancer control. However, the clinical utility of universal germline testing is unknown. Methods: The City of Hope INSPIRE study offers all consented patients GT for cancer susceptibility (155 genes) and actionable disorders (59 genes). We used an informatics approach to evaluate healthcare utilization for patients found to have BRCA1/ BRCA2 mutations. We queried codified data in our electronic data warehouse before and after GT (post testing interval: 1-29 months). We binned care as possibly related/ not related to HBOC based on NCCN guidelines. Results: Of 10,814 patients who had GT, 217 (2%) had a pathogenic/ likely pathogenic mutation in either BRCA1 or BRCA 2. The demographic distribution of mutation carriers was: white (n = 162, 75%), Asian (n = 28, 13%), Hispanic (n = 65, 30%); female (n = 184, 85%); the mean age was 54 yrs. Eighty-four percent (n = 182) had cancer, including 64% with cancers associated with HBOC (breast 40%, ovarian 13%, pancreatic 3%, 5% prostate, and 0.5% melanoma) and 18% with cancers that are not associated with HBOC. Eighty-three percent of patients had procedures, imaging, and/or therapy potentially related to the BRCA mutation. Eighty-six percent of cancer patients had potentially related care. As expected, use of breast MRI, mammography, MRCP, mastectomy, and bilateral salpingo-oophorectomy (BSO) occurred both before and after testing, with most utilization occurring prior to GT and likely related to cancer staging and treatment. The exception was MRCP which occurred more often following GT (0.6% before vs 1.2% after). Fifty-one (28%) cancer patients received PARP inhibitors. In the unaffected cohort, 67% of patients received possibly related care. Use of mammography was higher prior to GT (7% vs 2%). Consistent with the fact that some unaffected patients were likely known mutation carriers prior to consent, mastectomy was higher prior to GT (5% vs 0%) and BSO was equivalent before and after GT (1.8%). Use of breast MRI (9% vs 15%), MRCP (1.8% vs 3%) and transvaginal US (5% vs 7%) were all higher after GT. Conclusions: We found high levels of relevant healthcare utilization for BRCA mutation carriers in the context of universal GT. However, this initial informatics approach is limited because key information on prior GT and motivations for surgery (e.g., therapeutic vs prophylactic mastectomy) are not adequately captured in codified data. Codified EHR queries will need to be augmented by text mining and/or manual chart review to fully capture care and assess the clinical utility of system-wide genetic care delivery interventions.