Abstract P3-07-07: Prevalence of BRCA 1/2 germinal mutation among young women with breast cancer: Experience in a third level private center
Authors: Vazquez-Juarez Daniela , Serrano-Olvera Juan A , Noguez-Ramos Alejandro , Regalado-Porras Gabriela O , Lazaro-León Jesus M , Olivares-Beltran Guillermo , Gerson-Cwilich Raquel 
Published: March 2022

Abstract
BACKGROUND: Breast cancer (BC) in young women has a behavior and biology associated with an increased risk of recurrence and death. The diagnosis of MC in young women is strongly associated with the presence of genetic mutations, mainly in the BRCA gene. However, an association between the presence of inherited genetic mutations and prognosis has not been observed. OBJECTIVE: To describe the prevalence and analyze the clinical-pathological characteristics of women, &lt;50 years with BC, with and without BRCA germline mutation. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study of women &lt;50 years with BC with and without BRCA germline mutation who received treatment at a private third level Medical Center. RESULTS: During the period from January 1, 2015 to June 1, 2020, 807 women with a diagnosis of breast cancer were identified who received systemic treatment under adjuvant, neoadjuvant or palliative indication. Of these, 360 (44.6%) were 50 years old or younger. 53 women with BC &lt;50 years had the result of a genetic panel and are the ones that were included for the analysis. Median age was 40 years (27-50), 55% &lt;40 years old. The immunophenotype, according to the evaluation by immunohistochemistry of the hormonal receptors, Ki-67 and HER2/neu status, was luminal A like in 13 (24.5%) women, luminal B like in 18 (34%), luminal B like with overexpression of HER2/neu in 7 (13.2%), HER2/neu in 3 (5.7%) and in 12 (22.6%) cases it was triple negative. 30/53 women (56.6%), presented some mutation in the genetic panel. BRCA1 and/or BRCA2 9/30 (30%) mutation, all of them were pathogenic variants. Mutations other than BRCA in 21/30 (70%), of these 7/21 (33.3%) pathogenic (P) mutations in the ATM (2), MUTYH (2), TP53 (2) and PALB2 (1) genes. In 14/21 (66.7%) variants of uncertain significance (VUS) were identified. We did not observe an association between the clinicopathological characteristics and the BRCA mutational status or other genetic mutations, except for the high degree of differentiation (p = 0.04), being more frequent in the mutated group. There were no differences in disease-free time between BRCA mutated and non-mutated patients (p = 0.12). CONCLUSIONS: The prevalence of the BRCA germline mutation in women with BC &lt;50 years in our population was 30%. The clinical and biological characteristics and the disease-free time were not different among the group with and without BRCA germline mutation, or other genes.
BRCA GENETIC VARIANTS (n:9)IDGenProtein changeNCBI 1000Clinical risk4BRCA1c.1960A&gt;Tp.Lys654*rs80357355P16BRCA1c.815_824dupAGCCATGTGGp.Thr276Alafs*14rs387906563P38BRCA1c.211 A&gt;Gp.Arg71Glyrs80357382P8BRCA2c.658_659delp.Val220llefs*4rs80359604P25BRCA2c.6024dupGp.Gln2009Alafs*9rs80359554P24BRCA1ex9-12del c.548?PBRCA2c.6413T&gt;Ap.Val2138Asprs80358877VUS40BRCA2c.8988_8990delATAinsTTp.Leu2996Phefsrs397508027P42BRCA2c.5146_5149dep.Tyr1716LysFs*8rs276174854P49BRCA2c.6244delp.Leu2082fsrs1131691125PNO BRCA GENETIC VARIANTS (n:21)IDGENProtein changeNCBI 1000Clinical risk45ATMc.7502A&gt;Gp.Asn2501Serrs531617441VUS48ATMc.3663G&gt;Ap.Trp1221rs864622490P52ATMc.2839-3_2839delinsGATACTArs786202148PAPCc.1895T&gt;Cp.Ile632Thrrs587781360VUS3ATMc.6919C&gt;Tp.Leu2307Phers56009889VUSSMAD4c746_747delinsCCp.Gln249delinsPrors587782209VUS23BAP1c.623G&gt;Ap.Arg208Glnrs867416499VUS32BRIP1c.3088_3096dupp.Ala1030_Ser1032duprs1187782159VUS36CDKN2Ac.146T&gt;Cp.Ile49Thrrs199907548VUS5CHEK2c.1567C&gt;Tp.Arg523Cysrs149501505VUS30DICER1c.1798G&gt;Cp.D600HVUS22FANCMc.5832G&gt;Tp.Leu1944Phers201017015VUS41FHc.1481C&gt;Tp.Ala494Valrs752369363VUSTSC1c.2432G&gt;Ap.Arg811Glnrs761281095VUS11MLH1c.2219T&gt;Cp.Ile740Thrrs1044486319VUS12MUTYHc.1227_1228dupp.Glu4110Glyfs*43rs587780078P16MUTYHc.1227_1228dupp.Glu4110Glyfs*43rs587780078P20PALB2c.509_510delp.Arg17Ilefs*14rs515726123P14PMS2c.865T&gt;Ap.Phe2891lers771787834VUS47POLEc.4150C&gt;TVUS6RAD51Cc.492T&gt;Gp.Phe164Leurs573992101VUS17TP53c.604C&gt;Tp.Arg202Cysrs587780072VUS50TP53c.587G&gt;Cp.Arg196Prors483352697P43TP53c.587G&gt;Cp.Arg196Prors483352697PKDRc.1416A&gt;Tp.Gln472Hisrs1870377VUS
Citation Format: Daniela Vazquez-Juarez, Juan A Serrano-Olvera, Alejandro Noguez-Ramos, Gabriela O Regalado-Porras, Jesus M Lazaro-León, Guillermo Olivares-Beltran, Raquel Gerson-Cwilich. Prevalence of BRCA 1/2 germinal mutation among young women with breast cancer: Experience in a third level private center [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-07-07.