Abstract 1635P
Background
Assessment of germline BRCA1-2 pathogenic variants (gPV) is routinely recommended in Pancreatic Ductal Adenocarcinoma (PDAC) patients (pts), due to clinical-epidemiological relevance. Limited data are available on the prevalence of gPV in other cancer predisposition genes, including the DNA Damage Response (DDR) system.
Methods
Clinical data of consecutive PDAC pts, of any age and stage, tested with a multigene germline panel between January 2018 and March 2023 in five Italian Institutes were collected. A descriptive analysis of gPV (class 4 and 5) frequency, clinical variables and risk factors, was performed. Since gene panels did not overlap across all Institutes, it was difficult to properly estimate the real prevalence of gPV and to compare the clinical characteristics of all wild type with any-PV population, as screened pts/gene also varied (291-1200). Herein we report the best scenario that may result in rates underestimation.
Results
Among the 1200 pts included in the analysis, 169 (14%) had a gPV (any-PV). 23/73 genes had a gPV in ≥ 1 patient. Genes with a gPV in >1% of tested pts were ATM (36/1200 - 3.0%), BRCA2 (35/1200 - 2.9%), CDKN2A (23/942 - 2.4%), BRCA1 (18/1200 - 1.5%), CHEK2 (11/838 - 1.3%), and COL7A1 (5/447 - 1.1%). Characteristics of the main cohorts are shown in the table. The risk of having a genomic gPV was ≥9% in all the subgroups of pts considered for the different variables, including >73 years old pts (11%). Moreover, 25% of pts with age 41-50, 18% of obese pts and 21% of pts with PDAC/breast/ovarian/prostate cancer/melanoma family history harbored a gPV.
Table: 1635P
Patients’ characteristics [N (%)]
Wild Type1031 | Any Pathogenic Variant169 | BRCA1-2 53 | ATM36 | CDKN2A23 | |
Age | |||||
Median | 66 | 63 | 60 | 63 | 64 |
Range | 28-89 | 26-83 | 44-79 | 38-83 | 51-83 |
≤50 | 84 (8) | 24 (14) | 10 (19) | 5 (14) | 0 |
51-73 | 753 (73) | 122 (72) | 41 (77) | 25 (69) | 18 (78) |
≥74 | 194 (19) | 23 (14) | 2 (4) | 6 (17) | 5 (22) |
Gender | |||||
Female | 525 (51) | 79 (47) | 26 (49) | 14 (39) | 10 (43) |
Stage | |||||
I-II | 256 (27) | 32 (21) | 6 (12) | 12 (38) | 5 (26) |
III | 192 (20) | 31 (20) | 10 (19) | 8 (26) | 2 (11) |
IV | 511 (53) | 92 (59) | 36 (69) | 11 (36) | 12 (63) |
NA | 72 | 14 | 1 | 5 | 4 |
CA19.9 | |||||
Median≤35 | 648191 (22) | 73824 (17) | 9838 (18) | 3882 (6) | 1037 (44) |
>35 | 666 (78) | 113 (83) | 36 (82) | 29 (94) | 9 (56) |
NA | 174 | 32 | 9 | 5 | 7 |
Family history | |||||
Yes | 383 (41) | 103 (65) | 38 (75) | 21 (64) | 15 (79) |
No | 554 (59) | 55 (35) | 13 (25) | 12 (36) | 4 (21) |
NA | 94 | 11 | 2 | 3 | 4 |
NA: not available
Conclusions
Our study highlighted a remarkable prevalence of gPV in cancer predisposition and DDR genes in a large cohort of PDAC pts. These findings endorse the implementation of an extended multigene germline panel to be offered to all PDAC pts, irrespective of age, stage, and personal/family history.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
M. Reni.
Funding
Has not received any funding.
Disclosure
G. Giordano: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bayer; Financial Interests, Personal and Institutional, Financially compensated role: Servier, Amgen, Seagen, Novartis, Ipsen. M. Reni: Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly, Panavance, Celgene, AstraZeneca, Viatris, Merck Sharp & Dohme, Servier, Sotio, Baxter; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.
Resources from the same session
1634P - Extensive molecular profiling of KRAS wild-type versus KRAS mutant pancreatic ductal adenocarcinoma on 233 patients
Presenter: Jeanne Lena
Session: Poster session 22
1636P - Circulating tumor DNA (ctDNA) profile in patients (pts) with pancreatic cancer (PC): A multicenter experience and challenges for clinical application
Presenter: Francisco Muñoz i Carrillo
Session: Poster session 22
1637P - Early retention of KRAS mutations in cfDNA is an ominous sign for pancreatic cancer patients during chemotherapy: A prospective cohort study
Presenter: Chien-Jui Huang
Session: Poster session 22
1638P - The prognostic and predictive role of class III β-tubulin and hENT1 expression in patients with advanced pancreatic ductal adenocarcinoma
Presenter: Taha Koray Sahin
Session: Poster session 22
1639P - Feasibility of tumor genomic sequencing on tissue obtained from endoscopic ultrasound in patients with pancreatic cancer
Presenter: Vaia Florou
Session: Poster session 22
1640P - Response monitoring with ctDNA in metastatic pancreatic cancer
Presenter: Jinwoo Ahn
Session: Poster session 22
1642P - Prognostic impact of an immunomorphological signature integrating immune, fibroblastic and tumor markers in a series of 217 resected pancreatic adenocarcinoma patients
Presenter: Franck MONNIEN
Session: Poster session 22
1643P - Clinical outcomes of FOLFIRINOX as front-line therapy in patients with localized pancreatic adenocarcinoma: Asian retrospective study of 781 patients
Presenter: Kyunghye Bang
Session: Poster session 22
1644P - The mutation landscape and evolution pattern of liver or peritoneal metastasis in pancreatic cancer
Presenter: Guoliang Yao
Session: Poster session 22