Abstract 770P
Background
Ovarian cancer (OC) is the most lethal gynecologic cancer. BRCA1/2 genetic testing has a significant impact on OC prevention and treatment, but the role of other genes in hereditary OC is less understood. In this study we analyzed wild-type BRCA1/2 OC patients (pts) registered in our clinic.
Methods
Observational study characterizing the molecular contribution of non-BRCA1/2 genes to hereditary cancer. Survival outcomes were calculated by the Kaplan Meier method.
Results
Between January 2000 to December 2020, 5233 index pts consented in genetic testing, 502 (9.6%) of whom had OC diagnosis. Of these, 176 pts (35%) underwent BRCA1/2 testing only, while 326 pts consented in multigene panel testing (MGPT). BRCA1/2 detection rate was 17% (86/502), while the detection rate for non-BRCA genes was 28/ 326 (8,6%). Wild-type BRCA1/2 OC pathogenic variants (PV), were diagnosed in RAD51D, RAD51C, CHEK2, ATM, TP53 (low allelic fraction in an advanced pt with fallopian tube carcinoma), BRIP1 and MUTYH genes (Table). Median age at diagnosis of non-BRCA OC pts with a PV identified was 57,5 yrs (34-73). For a median follow-up of 42.7 months (7.9-254.2), 14 (50%) pts had recurrent disease and 5 (17.9%) pts died. Median progression free survival was 29.3 months (7.9-110.8) and median OS was 155.25 months (127-182). No significant difference was observed in OS between wild-type BRCA1/2 OC and the hereditary non-BRCA1/2 subgroup (p = 0.097). Survival differences between index BRCAmt and the hereditary non-BRCA OC were also non-significant(p=0.204). Table: 770P
| PV | n(%) |
| RAD51D | 9 (32.1) |
| RAD51C | 9 (32.1) |
| CHEK2 | 4 (14.3) |
| ATM | 2 (7.1) |
| RAD50 | 1 (3.6) |
| TP53* | 1 (3.6) |
| BRIP1 | 1 (3.6) |
| MUTYH | 1 (3.6) |
*low allelic fraction
.Conclusions
RAD51C and RAD51D genes are the main contributors to hereditary wild-type BRCA1/2 OC in our cohort. The identification by MGPT of a TP53 PV with low allelic fraction raises suspicion of somatic interference. Although most pts with PV in genes other than BRCA1/2 had either relapsed or died at the time of this analysis, no differences in survival were observed between this subgroup and BRCA1/2 wild-type OC neither with BRCA1/2 OC.
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.