Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial

Abstract

Background:Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)–based testing.Methods:In a randomized controlled trial of BRCA1/2 gene-mutation testing in the Ashkenazi Jewish (AJ) population, we compared testing all participants in the population screening (PS) arm with testing those fulfilling standard FH-based clinical criteria (FH arm). Following a targeted community campaign, AJ participants older than 18 years were recruited by self-referral after pretest genetic counseling. The effects of BRCA1/2 genetic testing on acceptability, psychological impact, and quality-of-life measures were assessed by random effects regression analysis. All statistical tests were two-sided.Results:One thousand, one hundred sixty-eight AJ individuals were counseled, 1042 consented, 1034 were randomly assigned (691 women, 343 men), and 1017 were eligible for analysis. Mean age was 54.3 (SD = 14.66) years. Thirteen BRCA1/2 carriers were identified in the PS arm, nine in the FH arm. Five more carriers were detected among FH-negative FH-arm participants following study completion. There were no statistically significant differences between the FH and PS arms at seven days or three months on measures of anxiety, depression, health anxiety, distress, uncertainty, and quality-of-life. Contrast tests indicated that overall anxiety (P = .0001) and uncertainty (P = .005) associated with genetic testing decreased; positive experience scores increased (P = .0001); quality-of-life and health anxiety did not change with time. Overall, 56% of carriers did not fulfill clinical criteria for genetic testing, and the BRCA1/2 prevalence was 2.45%.Conclusion:Compared with FH-based testing, population-based genetic testing in Ashkenazi Jews doesn’t adversely affect short-term psychological/quality-of-life outcomes and may detect 56% additional BRCA carriers.

When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer

“…These include young age of breast cancer diagnosis, bilateral breast cancer, 'triple negative' breast cancer or membership of ethnicities with founder mutations. 8,10,11 Marie-Claire King et al 12 have even suggested that all unaffected women aged 30 and over should be tested. Thus, increasingly women without a strong family history of breast cancer will be identified as mutation carriers.…”

“…Very few studies are currently available on the psychological impact of TFGT or traditional genetic testing for BRCA1/2 mutations in the subgroup of women with no knowledge of/minimal family history (FH), and the available studies are limited to Ashkenazi Jewish people participating in population-based screening. 11,17 This article describes a qualitative study that compared the impact of TFGT on psychological adjustment and associated unmet support needs in women with no knowledge of/minimal (FH − ) and with a strong family history (FH+).…”

Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper

“…They identified multiple factors of concern: lack of physician awareness of, or time, to fully assess family history, lack of patient acceptance, delays and/or denials by third party payers, variable availability of genetic counseling professionals, lack of reimbursement for genetics professionals, and racially and culturally disparate and/or underinsured populations (Table 2). Some providers may be concerned that there is a psychologically negative effect of being "labeled" as a mutation carrier, although most studies and experience refute this assertion [62][63][64][65][66][67]. In fact, most women and their families are empowered by informative results.…”

BRCA1/2 Population Screening: Embracing the Benefits

“…Thus, the genetic information provided was rapidly incorporated into health care decisions. Similarly, two recent studies from the United Kingdom also argued that population screening of Ashkenazi individuals was cost-effective, and again, 56% of identified mutation carriers would not have met family history criteria for genetic testing 11,12 .…”