The benefit of pancreatic cancer surveillance in carriers of germline BRCA1/2 pathogenic variants

Cancer. 2024 Jan;130(2):256-266. doi: 10.1002/cncr.35052. Epub 2023 Oct 20.

Abstract

Background: Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance.

Methods: A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC.

Results: A total of 180 asymptomatic carriers participated in the screening programs, including 57 (31.7%) with BRCA1 PVs, 121 (67.2%) with BRCA2 PVs, and 12 (6.6%) with PVs in BRCA1/2 and other genes, for a median follow-up period of 4 years. Ninety-one individuals (50.5%) fulfilled the International Cancer of the Pancreas Screening (CAPS) criteria for surveillance whereas 116 (64.4%) fulfilled the American College of Gastroenterology (ACG) criteria. There were four cases of adenocarcinoma and four cases of grade 1-neuroendocrine tumor (G1-NET). All were BRCA2 carriers, and two had no family history of PDAC. Three cancer patients were at resectable stages (IA, IIA, IIB) whereas one had a stage IIIB tumor. Of the G1-NET cases, one had surgery and the others were only followed. Success rate for detection of confined pancreatic carcinoma was thus 1.6% (three of 180) in the whole cohort, 1.6% (two of 116) among individuals who fulfilled ACG criteria and 2.2% (two of 91) in those fulfilling CAPS criteria for surveillance.

Conclusions: Despite the low detection rate of PDAC and its' high-risk neoplastic precursor lesions among BRCA1/2 carriers undergoing pancreatic surveillance, 75% of cancer cases were detected at a resectable stage.

Keywords: BRCA carrier; pancreatic cancer; surveillance.

Publication types

  • Multicenter Study

MeSH terms

  • Adenocarcinoma* / diagnosis
  • Adenocarcinoma* / epidemiology
  • Adenocarcinoma* / genetics
  • BRCA1 Protein / genetics
  • BRCA2 Protein / genetics
  • Carcinoma, Pancreatic Ductal* / diagnosis
  • Carcinoma, Pancreatic Ductal* / epidemiology
  • Carcinoma, Pancreatic Ductal* / genetics
  • Cohort Studies
  • Genetic Predisposition to Disease
  • Germ Cells
  • Humans
  • Pancreatic Neoplasms* / diagnosis
  • Pancreatic Neoplasms* / epidemiology
  • Pancreatic Neoplasms* / genetics

Substances

  • BRCA1 protein, human
  • BRCA1 Protein
  • BRCA2 protein, human
  • BRCA2 Protein