Abstract P2-09-14: Characteristics of TNBC patients carrying other than BRCA gene mutations
Authors: Cortesi Laura , Venturelli Marta , Toss Angela , Piombino Claudia , Barbieri Elena , Razzaboni Elisabetta , Moscetti Luca , Piacentini Federico , Omarini Claudia , Domati Federica , Dominici Massimo 
Published: March 2022

Triple-negative breast cancer (TNBC) represents approximately 10-20% of Breast Cancer (BC) diagnosed worldwide and in accordance with the current guideline it is defined by the absence of expression of the of expression of the estrogen receptor (ER&lt;1%), progesterone receptor (PR&lt;1%) and human epidermal growth factor 2-receptor (HER-2) amplification or overexpression. Up to 10-20% of TNBC patients (pts) are found to carry deleterious germline BRCA1/2 mutations and germline genetic testing is common practice in Modena Family Cancer Clinic (MFCC) since 1998. Many of the other genes involved in HR repair are now recognized to contribute to hereditary BC and/or ovarian cancer (OC) risk. Nowadays, the Italian Association of Medical Oncology (AIOM) guidelines recommend BRCA1/2 testing for patients meeting hereditary BC and/or OC or personal history of TNBC diagnosed before 60y while recommendations for testing of other genes are not fully established by National Guidelines. The aim of our study was to explore the high and moderate penetrance BC genes mutation rate in TNBC identified in the MFCC. Between 1998 and 2017, the MFCC offered BRCA1/2 genetic testing, while on January 2018, the Clinical Genomics Laboratory of the MFCC started to provide a Next Generation Sequencing (NGS) multigene panel (MGP) testing for 22 actionable genes (APC, ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53).For the purpose of our study, we retrospectively evaluated 274 TNBC patients underwent MGP testing in the last 42 months. In our study, 35 non-BRCA pathogenic or likely-pathogenic variant (PVs) were identified (12.8%). In details, we observed 16 PALB2 mutations (5.8%), 5 RAD51C/D mutations (1.8%), 3 ATM and MUTYH mutations (1.1%), 2 BRIP mutations (0.7%) and one mutation of PSM2, BARD1, CHECK2, TP53, NBN and PTEN genes (0.4%). Two pts carried 2 PVs together: BRCA and MUTYH, BRIP1 and TP53, respectively. Finally, 7 out of 34 pts (20.5%) were diagnosed at age &gt;=60yThe majority of BC was diagnosed at an early stage. All TNBCs present ductal histotype, mostly with high proliferation rate and grading 3. Characteristics of tumors are shown in Table 1. In our cohort, PALB2 mutations were the most frequent PVs in non-BRCA genes, in line with several previous studies. Interesting, we identified RAD51C/D mutations as second PVs non-BRCA genes, in support of certain studies that suggest an association with an increased risk for TNBC and OC. In conclusion, our results support the MGP using, opening the question about the 60-year cut off for genetic testing in TNBC, regardless of family history.

Table 1.Characteristics of TNBC tumors in patients carrying other than BRCA gene mutationsPALB2RAD51C/DATMMUTYHBRIPPMS2PTENNBNBARD1CHECK2TP53Number of patients165332111111Mean age at diagnosis (y)61.4 (44-94)48 (33-62)52.3 (49-54)44.3(40-50)42.5 (36-49)394958485036Ki 67 (%)&lt;405(45.5%)01(50%)1 (50%)0011000&gt;=406(54.5%)4(100%)1(50%)1 (50%)1(100%)100100unknown51111000011GradingG1-23 (25%)0000001000G39 (75%)4 (100%)3 (100%)3(100%)2(100%)110101Unknown41000000010Histotypeductal14 (100%)4(100%)3(100%)3(100%)2(100%)110111others00000001000unknown21000000000Stage at diagnosisI7 (63.6%)3 (60%)01 (100%)1 (100%)010000II4 (36.4%)1 (20%)2 (100%)00001000III01 (20%)000300000unknown50121000111

Citation Format: Laura Cortesi, Marta Venturelli, Angela Toss, Claudia Piombino, Elena Barbieri, Elisabetta Razzaboni, Luca Moscetti, Federico Piacentini, Claudia Omarini, Federica Domati, Massimo Dominici. Characteristics of TNBC patients carrying other than BRCA gene mutations [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 P2-09-14.