Cassandra B. Nichols

Routine Tumor Testing for Homologous Recombination Deficiency in Patients With High Grade Epithelial Ovarian Cancer at a Statewide Gynecological Cancer Service in Western Australia: An Observational Study

ABSTRACTBackgroundPoly‐ADP ribose polymerase inhibitors have been shown to improve progression‐free survival in patients with advanced high‐grade epithelial non‐mucinous ovarian cancers characterized by a deficiency in homologous recombination (HRD). Guidelines recommend all patients with advanced high‐grade epithelial ovarian cancer undergo genomic tumor testing for HRD. Our aim was to evaluate the first year of HRD testing at the statewide Western Australia Gynecologic Cancer Service to assess factors associated with obtaining a diagnostic HRD testing result.MethodsRetrospective chart review.ResultsHRD testing was indicated in 84 patients, and ordered in 79, of which three had non‐diagnostic/inconclusive results, all due to insufficient tumor quantity. One patient had the sample collected using a 20‐gauge core biopsy needle under image guidance, one patient following interval debulking surgery, and one following primary debulking surgery. Of 76 patients with an HRD result, HRD was positive in 29 (38.2%). A somatic BRCA mutation was detected in six of these 29 patients (20.6%) and HRD positive, BRCAwt was detected in 23 of 29 patients (79.4%). All core biopsies with 16‐ and 18‐gauge needles had a diagnostic HRD result. Ten of 11 patients who were treated by neoadjuvant chemotherapy and whose biopsies were obtained at interval cytoreductive surgery had sufficient tumor tissue for testing and had a diagnostic HRD result. All ascitic/pleural fluid samples sent for HRD testing yielded diagnostic results.ConclusionsCompliance with HRD testing was high, and only three of 79 (3.8%) patients had non‐diagnostic results.

Lynch syndrome associated endometrial carcinomas in Western Australia: an analysis of universal screening by mismatch repair protein immunohistochemistry

In 2016 universal screening with mismatch repair protein immunohistochemistry in all newly diagnosed endometrial carcinomas was introduced in Western Australia. To compare the prevalence of Lynch syndrome associated endometrial carcinomas between 2016 and 2019 with a historical control (2015). Additionally, to compare the number of cases appropriately referred for genetic assessment. A cross-sectional study of cases presented at the Western Australia gynecologic oncology tumor board was carried out. The primary outcome was the prevalence of Lynch syndrome associated endometrial carcinomas. A secondary outcome was the number of cases appropriately referred for genetic assessment. The following variables were extracted: date of birth; age at diagnosis; vital status; tumor mismatch repair protein expression status (retained or lost) and if lost, the specific mismatch repair protein deficiency; patients who were referred to a genetic clinic; and family history, if recorded. Data were collected from the clinical databases of the Familial Cancer Program at Genetic Services of Western Australia and WOMEN Center, to determine whether patients were appropriately referred for genetic evaluation and to ascertain the results of genetic testing. Between 2016 and 2019, there were 1040 new endometrial carcinomas. Tumors of 883 (85%) patients underwent mismatch repair protein immunohistochemistry compared with 117 of 199 patients (59%) in 2015 (χ Universal immunohistochemical screening did not increase the proportion of Lynch syndrome associated endometrial carcinomas identified, although the study was underpowered to detect small differences. There was an improvement in appropriate referrals for genetic assessment.

Incidence of germline BRCA1/2 mutations in women with tubo-ovarian high-grade serous carcinomas with and without serous tubal intra-epithelial carcinomas

To compare the germline A retrospective study was performed of patients in Western Australia diagnosed with high-grade serous tubo-ovarian and primary peritoneal carcinoma and referred for genetic counseling and A total of 269 women with high-grade serous tubo-ovarian and primary peritoneal carcinoma were referred for genetic counseling and testing. 114 patients were excluded because the serous tubal intra-epithelial carcinoma status was not assessable or because patients did not attend for genetic assessment. 155 patients (55 serous tubal intra-epithelial carcinoma-positive and 100 serous tubal intra-epithelial carcinoma-negative) underwent genetic testing. The