Multigene panel analysis in breast and ovarian cancer

Background: Genetic testing is of prognostic and predictive importance in patients with ovarian cancer and breast cancer. The best explored mutations are those of the BRCA 1 and BRCA2 genes, and the result of BRCA testing impacts treatment and prophylactic options. Data on other breast-cancer-associated genes are accumulating. Methods: All patients who underwent genetic counseling and testing for BRCA 1 and BRCA 2 between 2007 and 2019 at the Medical University of Graz were reviewed. If BRCA testing was negative patients were offered panel testing for other breast and ovarian cancer associated genes including ATM, PETEN, RAD50, RAD51D, RAD51C, TP53, STK11, ATM, NBN, CDH, MSH6, MSH2, MLH1, CHEK2, PALB2, BRIP1, SMO, PETEN, SMO. Results: In total 1905 patients were counseled for genetic testing between 2007 to 2019. In 292 patients (mean age 53yrs) panel gene testing was performed. 114 (39%) of these 292 BRCA-negative patients (55 with breast cancer, 24 with ovarian cancer) had a pathogenic variant (n=32) or a mutation of unknown significance (n=82). The most common pathogenic variant occurred in the CHEK2 gene (n=15). Interpretation: In this series approximately one third of high-risk patients who tested negative for a BRCA mutation had a mutation of unknown significance and/or pathogenic mutation in gene panel testing. This indicates that genetic panel testing should be considered more frequently. Citation Format: Elisabeth Katharina Trapp, Michael Speicher, Jochen B Geigl, Vassiliki Kolovetsiou-Kreiner, Julia Reisinger, Josef Haas, Edgar Petru, Karl Tamussino, Gunda Pristauz. Multigene panel analysis in breast and ovarian cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-03-09.