Abstract PS8-19: High rates of BRCA1 and BRCA2 variants of uncertain significance (VUS) among Jordanian breast cancer patients
Authors: Abdel-Razeq Hikmat , Tamimi Faris , Abujamous Lama , Khashabeh Razan Abu 
Published: February 2021

Abstract
Background: Contrary to pathogenic BRCA mutations, recommendations for management of Variants of Uncertain Significance (VUS) is not clear and focus more on clinical factors, personal and family history of cancer; breast and ovarian in particular. Genetic variants that may or may not have clinical consequence can be confusing and anxiety-provoking to patients and physicians, alike. No data exist on Arab patients with VUS mutations. In this study we search for the frequency of VUS among high risk breast cancer patients tested for BRCA mutations and study risk-reduction interventions related to such findings. Methods: We utilized an institutional database started January 2015 for all patients with breast cancer tested for BRCA mutations as per the National Comprehensive Cancer Network (NCCN) guidelines, including those with early onset cancers, triple-negative disease and positive family history. We also reviewed surgical interventions patients had in relation to their breast cancer and VUS mutation identification. RESULTS: Between January 2015 and May 2020, a total of 1181 patients were tested for BRCA1 and BRCA2 mutations as per the NCCN guidelines. Pathogenic mutations were detected in 134 (11.3%) patients, while 109 (9.2%) others had VUS; 79 (72.5%) were in BRCA2. At time of testing, all VUS patients had breast cancer; 7 (6.4%) with metastatic disease. Median age (range) was 39 (25-66) years with 63 (57.8%) were 40 years or younger at diagnosis. Twelve (11.0%) had triple negative disease while 14 (13.1%) others had bilateral or two or more unilateral primary breast cancers. Family history of breast, ovarian or pancreatic cancers, in at least one close relative, was identified in 52 (47.7 %) patients. Among 101 patients with nonmetastatic disease, 48 (48.0%) had breast conserving surgery (BCS) while only 5 (5.0%) had bilateral mastectomies, all were due to bilateral disease and not prophylactic. VUS diagnosis was known prior to initial surgery in 33 (32.7%) patients; 11 (33.3%) of them had lumpectomy only. Since we started genetic testing 5 years ago, there is a slight decline in VUS rate but none of the VUS reported mutations so far were reclassified. Conclusions: Despite significant decline in VUS rates reported in the western societies, our rate continues to be high and alarming. Our knowledge of VUS had not significantly impacted on therapeutic or prophylactic surgical decisions. Given the relatively high rate of second breast cancers among such patients, management should be dictated by their personal or family history. A regional (Arab) VUS registry and comprehensive genetic counseling to ensure appropriate follow up and understanding by affected patients, are highly needed.
Citation Format: Hikmat Abdel-Razeq, Faris Tamimi, Lama Abujamous, Razan Abu Khashabeh. High rates of BRCA1 and BRCA2 variants of uncertain significance (VUS) among Jordanian breast cancer patients [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 PS8-19.