Abstract 1867P
Background
Pathogenic variants (PV) in RAD51C have only been modestly associated with breast cancer (BC) risk. To date, there is little information regarding the frequency of RAD51C PV in Mexican women with BC that undergo genetic cancer risk assessment. Moreover, there is scarce data about the family history (FH) and age at BC diagnosis of RAD51C PV carriers as compared to BRCA1/2 carriers.
Methods
Medical records of women with BC from two centers in Monterrey, Mexico who underwent a next-generation sequencing panel for BC predisposition genes (APC, ATM, BRCA1, BRCA2, BRIP1, CHEK2, CDH1, CDKN2A, MLH1, MSH2, MSH6, MUTYH, NF1, PALB2, PMS2, PTEN, RAD50, RAD51C, RAD51D, TP53) based on NCCN recommendations were reviewed. Patients with germline PV in BRCA1/2 or RAD51C were considered eligible.
Results
Between 2014 and 2020, a total of 5 RAD51C (1.1%), 48 BRCA1 (11.0%), and 24 BRCA2 (5.5%) PV carriers were identified from 437 BC cases. FH and mean age at BC diagnosis are shown in the table. Two previously described RAD51C PV were identified: RAD51C c.577C>T (p.Arg193Stop) PV in exon 4 (present in an index case with bilateral BC without FH of BC or ovarian cancer [OC], as well as in three cases with FH of BC+OC) and RAD51C intronic c.404+2T>C PV (present in an index case with FH of BC). Cascade testing was possible in two families, one with no additional carriers (three maternal cousins with BC were tested) and one in which three additional RAD51C PV carriers were identified (two with a BC diagnosis and one with no BC history). Table: 1867P
Family history and mean age at BC diagnosis in carriers of BRCA1/2 and RAD51C pathogenic variants
| Gene | FH of BC | FH of BC and OC | No FH | Mean age at BC diagnosis |
| BRCA1 | 24 | 13 | 11 | 48.2 |
| BRCA2 | 14 | 7 | 3 | 35.3 |
| RAD51C | 1 | 3 | 1 | 39.2 |
Conclusions
The prevalence of RAD51C PV in our cohort was higher than previously reported in the literature. Future studies are warranted to characterize the clinical significance of RAD51C-associated BC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.