Geographic and Ethnic Heterogeneity of Germline BRCA1 or BRCA2 Mutation Prevalence Among Patients With Metastatic Pancreatic Cancer Screened for Entry Into the POLO Trial

J Clin Oncol. 2020 May 1;38(13):1442-1454. doi: 10.1200/JCO.19.01890. Epub 2020 Feb 19.

Abstract

Purpose: Germline BRCA1 and/or BRCA2 mutations (gBRCAms) are risk factors for pancreatic cancer. The extent to which demographic and geographic factors affect the uptake of gBRCAm testing in pancreatic cancer (PC) is unknown.

Methods: We conducted a retrospective, descriptive analysis of demographic/geographic data from the first 2,206 patients with metastatic PC (mPC) screened for eligibility to enter the phase III POLO trial of maintenance olaparib. No formal statistical tests were performed.

Results: Of 2,167 patients with previously unknown gBRCAm status, 128 (5.9%) had a newly identified gBRCAm; rates were highest in the United States, France, and Israel (9.5%, 7.6%, and 7.4%, respectively). When including patients with a previously known gBRCAm, prevalence rose to 7.2% (or 5.8% after excluding populations enriched in Ashkenazi Jews, who are known to have a high rate of BRCA1 and BRCA2 founder mutations). Patients with a gBRCAm were slightly younger (57.9 v 61.1 years) and more likely to have early-onset mPC than those without. Higher newly identified gBRCAm prevalence was observed among African American (n = 28) versus white (n = 1,808), Asian (n = 218), and other (n = 61) patients (10.7% v 6.1%, 5.0%, and 1.6%, respectively). Of 139 white patients with a gBRCAm, 110 were newly identified during screening; the majority of gBRCAms in African American, Asian, and Hispanic patients (n = 3, n = 11, and n = 5, respectively) were newly identified.

Conclusion: We identified substantial geographic and some racial variability in gBRCAm prevalence among patients with mPC, an important consideration given the increased use of familial screening and possible future use of targeted therapies in this setting. Although our study included small numbers of nonwhite patients, prior knowledge of their gBRCAm status was limited compared with their white counterparts, which suggests disparities in genetic testing uptake.

Trial registration: ClinicalTrials.gov NCT02184195.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Australia / epidemiology
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Canada / epidemiology
  • Female
  • Genetic Testing / methods*
  • Germ-Line Mutation*
  • Humans
  • Israel / epidemiology
  • Jews / genetics*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / epidemiology
  • Pancreatic Neoplasms / genetics*
  • Prevalence
  • Retrospective Studies
  • United States / epidemiology

Substances

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

Associated data

  • ClinicalTrials.gov/NCT02184195