Abstract P6-02-01: Frequency of pathogenic germline mutations beyond Germline BRCA gene mutations among Saudi patients with breast cancer

Abstract Frequency of pathogenic germline mutations beyond Germline BRCA gene mutations among Saudi patients with breast cancer Mohammed Algarni*1,2,3, Ashwaq Alolayan1,2,3, Fouad Sabatin1,2,3, Nadine Mabsout1, Horya Zaher1, Hussam Shehata1, Saeed Alturki4, Abdulaziz alshalhoub1, Fatimah Alturki1, Sadal Refaea1,2,3, Nafisah Abdelhafiz1,2,3, Turki Alfayea 1,2,3, Mohammed Al Balwi1,2,3 Kanan Alshammari1,2,3 1King Abdulaziz Medical City, Ministry of National Guard – Health Affairs, Riyadh, Saudi Arabia, 2King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia, 3King Abdullah International Medical Research Center, Riyadh, Saudi Arabia 4Anwa lab Riyadh, Saudi Arabia Background : Breast cancer is the commonest cancer diagnosed in the kingdom of Saudi Arabia. Although the majority of breast cancer cases are sporadic, around 25-30% are related to hereditary and familial components. Germline BRCA gene mutations are most common mutations associated with hereditary breast cancer predisposition syndromes. In Saudi Arabia, the reported frequency of germline BRCA mutations is 11%1,2. There is no data about the prevalence non BRCA pathogenic germline mutations in Saudi population. We aimed to study the prevalence of these mutations in Saudi patients with breast cancer. Methods : We analyzed all the confirmed breast cancer cases who were referred to the cancer genetic clinic at King Abdulaziz medical city in Riyadh, Kingdom of Saudi Arabia by using our cancer genetics database. Since November 2018, a comprehensive hereditary cancer gene panel is offered to all referred breast cancer cases who meet the NCCN testing guidelines after obtaining a genetic counselling assessment and an informed consent. All testing was internally funded by the institution.The comprehensive panel tested genes are; ABRAXAS1, APC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, DIS3L2, EPCAM, FANCC, FH, FLCN, GALNT12, HNF1B, HOXB13, KIT, MC1R, MEN1, MET, MITF, MLH1, MLH3, MRE11, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PMS1, PMS2, POLD1, POLE, POT1, PRSS1, PTCH1, PTEN, RAD50, RAD51C, RAD51D, RECQL, RET, RNF43, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, TGFBR2, TP53, TSC1, TSC2, VHL, WT1, XRCC2, XRCC3. Result : Between November 2018 and May 2022, a total of 332 patients with breast cancer have been tested. The median age was 45 and 54 years for females and males, respectively. The majority of patients were females (n=322, 97%). Most of the patients had stage III disease (n=183, 55%) followed by stage II(n=91, 27%). Pathogenic variant(PVs) was reported in 16% (n= 52), variant of uncertain significance (VUSs) was reported in 10% (n=32) while no mutation reported in the rest of the patients. TNBC was the most common phenotype among carriers of pathogenic mutation (50%). The PVs reported were BRCA1 (n= 19),BRCA2 (n= 21), PALB2(n= 2), PTEN (n= 2), ATM(n= 1), BARD1(n= 1), BLM(n= 1), BRIP1(n= 1), CDKN2A(n= 1), CHECK2(n= 1), MSH2(n= 1) and RECQL(n= 1). Conclusion : This study shows that extended panel testing beyond BRCA gene increases the rate of detection of pathogenic germline mutations that has preventative and possibly therapeutic implications. In addition, to the best of our knowledge this is the first study that gives insight about the frequency of non germline BRCA mutations which represent unmet needs for breast cancer patients in Saudi Arabia. 1. J Glob Oncol. 2018 Aug;4:1-9. 2. Breast Cancer Res Treat. 2018 Apr;168(3):695-702 Citation Format: Ashwaq Alolayan, Fouad Sabatin, Mohammed algarni, Nadine Mabsout, Horya Zaher, Hussam Shehata, Saeed Alturki, Abdulaziz Alshalhoub, Fatimah Alturki, Sadal Refaea, Nafisah Abdelhafiz, Turki Alfayea, Kanan Alshammari, Mohammed Albalwi. Frequency of pathogenic germline mutations beyond Germline BRCA gene mutations among Saudi patients with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-01.