Recontacting non-BRCA1/2 breast cancer patients for germline CHEK2 c.1100del pathogenic variant testing: uptake and patient experiences

Abstract

Background CHEK2 has been recognized as a breast cancer risk gene with moderate effect. Women who have previously tested negative for a BRCA1/2 gene germline pathogenic variant may benefit from additional genetic testing for the CHEK2 c.1100del pathogenic variant. The aims of this study were: 1) to assess the uptake of an active approach by recontacting BRCA1/2-negative women for additional CHEK2 c.1100del testing on stored DNA-samples and 2) to explore patients’ experiences with this approach. Methods Between 2015 and 2017, women who had been tested earlier negative for BRCA1/2 germline pathogenic variants, were recontacted for additional CHEK2 c.1100del testing on stored DNA-samples, free-of-charge. They received an information letter about the CHEK2 pathogenic variant and could return an informed consent form when they opted for additional genetic testing. Those in whom the CHEK2 pathogenic variant was absent, received a letter describing this result. Those who tested positive, were invited for a personal counseling at the department of genetics. On average 21 months (range 4–27) after the genetic test result, a questionnaire was sent to all identified carriers and a control group of women who tested negative for the pathogenic variant to explore patients’ experiences with our approach. Results In total, 70% (N = 1666) of the N = 2377 women contacted opted for additional testing, and 66 (4%) of them proved to be carriers of the CHEK2 c.1100del pathogenic variant. Regardless of the outcome of the genetic test, women were generally satisfied with our approach and reported that the written information was sufficient to make an informed decision about the additional CHEK2 testing. Conclusions The uptake (70%) of our approach was considered satisfactory. Patients considered the benefits more important than the psychosocial burden. Given the rapid developments in DNA-diagnostics, our findings may support future initiatives to recontact patients about additional genetic testing when they previously tested negative for a pathogenic variant in a breast cancer gene.

Parental experiences of recontacting for extended genetic testing after a terminated pregnancy for congenital malformations

“…These participants did not express negative feelings about being recontacted despite the unexpectedness of the contact and the potential past di culties of coping with a TOP. Previous studies also con rmed mainly positive attitudes towards recontacting (17)(18)(19)(20)(21)26). However, the number of qualitative studies exploring in depth the experience of being recontacted is scarce.…”

“…A few studies have been published in patients with different genetic conditions, more speci cally in deceased children with a mitochondrial disorder (19), children with intellectual disability (18), hereditary cancer patients (20) and patients with varying genetic disorders (21). In general, these empirical studies describe a mainly positive feeling (17)(18)(19)(20)(21), however more indepth exploration of patients' experiences with recontacting is lacking. On the contrary, personal motivations for pursuing genetic testing have been extensively investigated in other contexts such as patients with Huntington's disease and hereditary cancer syndromes.…”

“…However, studies from a patient perspective are rather scarce. A few studies have been published in patients with different genetic conditions, more speci cally in deceased children with a mitochondrial disorder (19), children with intellectual disability (18), hereditary cancer patients (20) and patients with varying genetic disorders (21). In general, these empirical studies describe a mainly positive feeling (17)(18)(19)(20)(21), however more indepth exploration of patients' experiences with recontacting is lacking.…”

Systematic review of the molecular basis of hereditary breast and ovarian cancer syndrome in Brazil: the current scenario

“…However, of the 14 studies that included the CHEK2 gene for screening in this review, only three were identified the c.1100delC variant [ 16 , 18 , 44 ]. This mutation has been described in less heterogeneous populations, as in studies conducted in the Netherlands that described the increased risk of breast cancer observed in patients with CHEK2 1100delC and another study that reported 4% of their tested patients carrying this pathogenic variant [ 64 , 65 ]. Studies show that carriers with a family history of breast cancer are at 2–3 times greater risk when breast cancer is associated with the CHEK2 c.1100delC mutation [ 66 ].…”