Abstract P6-02-05: Prevalence of non-BRCA germline pathogenic variants in Mexican women with breast cancer referred for genetic cancer risk assessment
Authors: Chavarri-Guerra Yanin , Garza Cynthia Villareal , Rodriguez-Olivares Jose Luis , Aguilar-y Mendez Dione , Quintero-Beulo Gregorio , Gutierrez-Delgado Francisco , Herzog Josef , Gruber Stephen 
Published: March 2023

Background:  The prevalence of germline pathogenic variants in Mexican women with breast cancer who met the reference criteria for genetic cancer risk assessment (GCRA) has been previously reported as close to 20%. However, information regarding the spectrum of gPVs in genes other than BRCA in this population is limited. Methods: This prospective study included Mexican women who were diagnosed with BC and met international criteria for GCRA. Participants were enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry and at two referral breast cancer centers in Mexico, the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City and at the Hospital Zambrano Hellion TecSalud, Monterrey. Participants underwent multigene panel testing (MGPT) for 37 cancer susceptibility genes. For this analysis, only the results of pathogenic and likely pathogenic variants in the index cases were reported. The demographic and molecular characteristics of the variants are described here. Results: From August 2017 to September 2021, 1020 Mexican women with BC underwent MGPT, with a median age at diagnosis of 41 y (range 20-86), of whom 206 (20.2%) were carriers. 208 gPVs were identified with BRCA1/2 representing 70% (145/208) of the gPVs (BRCA1 n=89, BRCA2 n=56). 63 (30%) of gPVs were identified in genes other than BRCA (CHEK2 n=21, PALB2 n=13, TP53 n=7, RAD51C n=5, ATM n=4, NF1 n=3, PTEN n=2, MUTYH homozygous n=2, RAD50 n=1, BRIP1 n=1, CDH1 n=1, NBN n=1, MSH2 n=1 and MSH6 n=1). The recurrent variants previously proposed as founders in the Hispanic population were frequent among those identified in their respective genes: CHEK2 c.707T&gt;C 81% (17/21), PALB2 c.2167_2168delAT 46% (6/13) and BRCA1 del(exons 9-12) 18% (16/89). As a group, the 4 most frequent genes where gPVs were identified (BRCA1, BRCA2, CHEK2 and PALB2) represented 86% (179/208) of the positive results. Conclusion: Among the variants identified in this population of Mexican women with BC, the proportion of gPVs in genes other than BRCA was significant (about 1 out of 3 pts), which justifies the use of MGPT in the assessment of our population. However, a tailored panel (sequencing of BRCA1/BRCA2/CHEK2/PALB2 and MLPA for BRCA1) could be proposed in areas of Mexico with limited medical resources, including the analysis of other genes in selected patients according to clinical suspicion and family history of cancer.

Citation Format: Yanin Chavarri-Guerra, Cynthia Villareal Garza, Jose Luis Rodriguez-Olivares, Dione Aguilar-y Mendez, Gregorio Quintero-Beulo, Francisco Gutierrez-Delgado, Josef Herzog, Stephen Gruber. Prevalence of non-BRCA germline pathogenic variants in Mexican women with breast cancer referred for genetic cancer risk assessment [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 P6-02-05.