The uptake of presymptomatic genetic testing in hereditary breast-ovarian cancer and Lynch syndrome: a systematic review of the literature and implications for clinical practice

Abstract

Following the identification in a proband of a germline BRCA1/BRCA2 mutation in hereditary breast-ovarian cancer (HBOC) or a DNA mismatch repair gene mutation in Lynch syndrome (LS) he or she will be asked to inform at-risk family members about the option for presymptomatic DNA testing. However, in clinical practice multiple factors may complicate the process of information sharing. We critically evaluated studies on the uptake of presymptomatic genetic testing in both syndromes. A search of relevant MeSH terms and key words in PubMed, Embase and PsycINFO yielded 795 articles published between 2001 and 2017. Thirty of these publications included outcome measures relevant for the current study. Based on information provided by the proband (15 studies) the uptake of presymptomatic genetic testing ranged from 15 to 57% in HBOC, while one study in LS kindreds reported an uptake of 70%. Based on information provided by genetics centres (the remaining 15 studies) the uptake ranged from 21 to 44% in HBOC and from 41 to 94% in LS. However, when genetics centres contacted relatives directly a substantial number of additional family members could be tested. Proband-mediated provision of information to at-risk relatives is a standard procedure in hereditary breast-ovarian cancer and Lynch syndrome. However, the resulting uptake of presymptomatic testing is disappointing-an issue that is now urgent due to the increased use of genetic testing in clinical oncology. We propose that additional strategies should be introduced including the geneticist directly contacting relatives. The outcomes of these strategies should be carefully monitored and evaluated.

Evaluating the impact of universal Lynch syndrome screening in a publicly funded healthcare system

“…Programs may consider this when developing outreach and educational material for patients. The need for more robust rates of cascade carrier testing in hereditary cancer has recently been called for, 29,30 and requires renewed energy by programs to examine outreach and services for this highest risk population. The diagnosis of the index patient is only one portion of a hereditary cancer program's goal to reduce morbidity and mortality related to LS in a given jurisdiction.…”

Epithelial ovarian cancer risk: A review of the current genetic landscape

“…The reasons for this are likely multifactorial, including insufficient referrals to clinical genetics, variable reporting of relatives by probands, inadequate understanding and communication of tests, feelings of irrelevance and deferring the process by relatives. [100][101][102] The use of screening has been investigated. The risk of ovarian cancer algorithm (ROCA) using serum CA125 and transvaginal ultrasound has been proposed for high-risk women; however, impact on survival is not known.…”

“…When a pathogenic variant is identified, it is essential that affected women are offered risk‐reduction interventions and cascade testing be offered to relatives. Uptake of cascade testing in this situation has been noted to be relatively low, estimated at 15% to 57% in one systematic review and genetic testing in eligible women with ovarian cancer also low. The reasons for this are likely multifactorial, including insufficient referrals to clinical genetics, variable reporting of relatives by probands, inadequate understanding and communication of tests, feelings of irrelevance and deferring the process by relatives .…”

Challenges and Opportunities for Cancer Predisposition Cascade Screening for Hereditary Breast and Ovarian Cancer and Lynch Syndrome in Switzerland: Findings from an International Workshop

“…Some of the most important barriers to delivering cascade screening include suboptimal communication between the proband and family members as well as geographic barriers for obtaining genetic services [3]. One suggestion to overcome communication barriers would be the development of new strategies for directly contacting relatives [34]. A healthcare professional could contact at-risk relatives with the permission of the proband, and this could be more successful than relying on the proband to make these referrals [35-37].…”

“…HBOC and LS cascade genetic testing performed outside structured screening programs is less successful because it relies completely on the willingness of probands to notify relatives [34]. On average less than 52% of first-degree relatives and less than 3.6 relatives per proband have been shown to receive genetic testing [51].…”