Abstract 765P
Background
BRCA1 and BRCA2 are tumour suppressor genes associated with the hereditary breast and ovarian cancer syndrome (HBOC). Previous data regarding BRCA1/2 penetrance estimated a median cumulative risk of ovarian cancer (OC) by 70 years of 25-40% and 11-18% for BRCA1 and BRCA2 carriers, respectively. In contrast to other populations, HBOC Portuguese patients (pts) have a higher prevalence of BRCA2 mutations, partially due to the effect of the founder BRCA2: c.156_157insAlu. In this study, we analyse the effect on prognosis of BRCA1 and BRCA2 variants in a Portuguese OC cohort.
Methods
In our centre, all pts with a BRCA1/2 positive test are invited to participate in an observational prospective registry. For this study, all BRCA1/2 cancer pts with a diagnosis of OC (either as first or after a previous neoplasia) identified between January 2000 and December 2020, were included. Statistical analysis was performed to compare the prognosis between BRCA1/2 and wildtype (wt), as well as between BRCA1 and BRCA2 OC pts.
Results
Between January 2000-December 2020, 5233 index pts consented in genetic testing. Of these, 502 had OC and 86 (17%) tested positive for a BRCA1/2 pathogenic variant. The global detection rate was higher (33,7%) until 2014 (when only OC pts with positive family history were tested), than after this date (13,4%), when we started testing unselected OC pts. Adding to the 86 index pts, 21 OC HBOC relatives were confirmed, for a total of 107 subjects: 52 BRCA1 (48,6%) and 55 BRCA2 (51,4%). OC was primary diagnosis in 79 pts (73,8%) and subsequent cancer in 28 pts (26,2%). For a median follow-up of 44,0 months (18–76), 59 pts (55,1%) are alive (24 BRCA1 and 35 BRCA2), with a trend to better overall survival (OS) for BRCA2 pts (46,2% vs 63,6%, p=0.069). No significant difference in OS was observed for OC as first or subsequent diagnosis (55,7% vs 53,6%, p=0.846). BRCA1/2 pts had significantly lower OS than wt pts (55,1% vs 66,3%, p=0.032), at the cost of worse BRCA1 outcomes (46,2% vs 66,3%, p=0.004).
Conclusions
In our cohort, BRCA2 variant contributed for more than half of the cases. A trend to better survival for BRCA2 vs BRCA1 pts was observed. Significantly lower OS for BRCA1/2 OC pts when compared with wt-OC was observed, at the cost of worse BRCA1 OC pts survival.
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.