Abstract 4628
Background
Gastric cancer (GC) risk is associated with Tp53 and ATM mutations but the inclusion of GC in the BRCA2 phenotype is still controversial due to confounding risk factors. Because of the high incidence of GC in Portugal and as 2/3 of all our HBOC families are BRCA2, to include or not GC surveillance in prospective follow up is of utmost importance. The objective of this study is to characterize GC diagnoses observed in a prospective cohort of BRCA1/2, Tp53 and ATM carriers to gain insight for future studies.
Methods
Review of all GC diagnoses in BRCA1/2, TP53 and ATM carriers under prospective surveillance and analysis of family data regarding GC.
Results
Data from 830 pts, 723 with a confirmed genetic diagnosis (BRCA2-488, BRCA1-205 Tp53-15, ATM-14, BRCA1/2-1pt) belonging to 534 non-related families (BRCA2-325, BRCA1-187, Tp53-12, ATM-9, both BRCA1/2-1) was reviewed. GC was reported in 15 BRCA1 (8%), 52 BRCA2 (16%), 4 ATM (44%) and 4 Tp53 (33%) families. More than 1 GC case was reported in 20%, 12%, 50%, 25% of BRCA1, BRCA2, ATM and Tp53 families, respectively. Pathological confirmation was available in 12 pts: 10 BRCA2 (2 GEJ, 60% male, median age at diagnosis 59,4 yrs), 1 ATM (male, 74 yrs), 1 p53 (female, 42 yrs). Pathology: 5 intestinal type, 2 signet ring cells, 4-other (including 1 NE tumor). Only five of 12 pts had GC as the only neoplastic diagnosis. For a median follow up of 39 months, 5 pts (42%) are alive, only 2 without relapse. Only 1 pt with signet ring cell GC was submitted to CT and an objective response was observed. GC was the cause of 71% of deaths.
Conclusions
Confirmed GC in BRCA2 carriers revealed a high morbidity and mortality. Unexpected response to platin therapy was observed in a signet ring cell case. Since management of BRCA2 carriers include measures that impact on survival, clarification of BRCA2 association with GC is necessary for better prospective surveillance plans, and eventually personalized therapeutic approaches.
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.
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