Abstract P4-14-06: Express model of hereditary multigene mutation analysis in breast cancer patients

Introduction Traditionally, women with family history of breast and ovarian cancer, or young age at presentation, are referred to BRCA1\2 mutation testing. The growing information regarding other genes involved in predisposition to breast cancer (regardless of specific family history) and the potential impact of germline alterations on surgical and oncologic management led us to establish a model to perform a quick multigene mutation evaluation among breast cancer patients at our cancer institute. Methods All breast cancer patients that required genetic counselling (according to treating oncologist/surgeon’s judgement) were referred, after thorough explanation and signing informed-consent forms, to a 9genetic coordinator9 and 9genetic nurse9. They provided each patient with a second pre-test explanation and ordered wide hereditary cancer gene panel (83-genes, Invitae). Results were given within 2-4 weeks. All patients\results were registered centrally at our center and discussed at routine Onco-genetic Multidisciplinary Board (OMB). A referral for formal genetic counselling is offered to all patients, and rapid track is arranged for patients with positive results. Results During a 12-months pilot period, 130 breast cancer patients were examined via the model, and 109 results were received; 44 patients (41%) had no abnormal findings, 50 patients (45%) had variants of uncertain clinical significance, and 15 patients (14%) were found carriers of pathogenic variants (ATM n=2, BRCA1 n=1, BRCA2 n=2, CHEK2 n=3, MUTYH n=1, PALB2 n=2, RAD50 n=1, RECQL4 n=1, TP53 n=2). Among this group, 3 patients (20%) had immediate panel-driven treatment decisions: Mastectomy to avoid radiotherapy (RAD50 carrier), oophorectomy during lumpectomy (BRCA2 carrier), and bilateral risk-reducing mastectomy instead of lumpectomy (TP53 carrier). Conclusions The creation of an Express-model for broad germline analysis allows to obtain rapid and meaningful results with impact on treatment. We believe that the Express-model should be considered as an integral tool of multimodal care of breast cancer patients. Citation Format: Albert Grinshpun, Einat Carmon, Luna Kaduri, Aviad Zick, Shiri Shkedi, Edna Shalom, Avital Granit, Liza Monas, Tamar Shaldovsky, Tamar Hamburger, Vardiella Meiner, Tamar Peretz. Express model of hereditary multigene mutation analysis in breast cancer patients [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 P4-14-06.