“I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants

Abstract

Little is known about what uncertainties patients experience after being identified to carry a pathogenic variant in a moderate-risk cancer gene as a result of undergoing multigene panel testing for cancer susceptibility. Data regarding cancer risk estimates and effectiveness of risk management strategies for these variants continues to evolve, which has the potential to evoke uncertainty. Acknowledging uncertainty during pre-and post-test discussions is imperative to helping individuals to adapt to their results. A better understanding of this population's experience of uncertainty is needed to facilitate such discussions and is the aim of the current study. Semi-structured interviews (30-60 min in length), informed by Han and colleagues' taxonomy of uncertainty in clinical genomic sequencing, were conducted to assess motivations to pursue genetic testing, areas of perceived uncertainty, and strategies for managing uncertainty among 20 carriers of pathogenic variants in two moderate-risk genes, ATM and CHEK2. We found that participants pursue genetic testing with the expectation that results will clarify cancer risks and approaches to management. Participants experience uncertainties aligning with Han's taxonomy relating to the ambiguity of specific cancer risk estimates and effectiveness of certain risk management strategies. These uncertainties influenced decisions around the uptake of risk management strategies, which were additionally impacted by clinicians' uncertainty towards such strategies. Participants employ a variety of uncertainty management approaches to cope with their anxieties. Clinicians may wish to use these findings to facilitate patient adaptation to the implications of multigene panel testing for cancer susceptibility during both pre-and post-test counseling sessions.

“You Always Have It in the Back of Your Mind”—Feelings, Coping, and Support Needs of Women with Pathogenic Variants in Moderate-Risk Genes for Hereditary Breast Cancer Attending Genetic Counseling in Germany: A Qualitative Interview Study

“…Since BRCA1/2 pathogenic variants are associated with a higher cancer risk, it may comfort some women that the test result is negative. This finding is in line with Reyes et al [ 22 ], who recently studied the uncertainty experienced by carriers of ATM and/or CHEK2 pathogenic variants. Participants of this study also reported relief due to the relatively lower risk of developing BC compared to individuals with pathogenic variants in high-risk genes, such as BRCA1/2 .…”

“…Since carrying a pathogenic variant is also something that one must accept and cannot change, the result of our study is in line with this assumption. Having an increased risk for hereditary BC implies being confronted with and challenged by uncertainty for a lifetime [ 22 , 47 , 48 ]. Studies even suggest that women who carry a pathogenic variant in an MBCG experience higher levels of uncertainty compared to carriers of a pathogenic variant in the high-risk genes BRCA1/2 [ 20 , 22 , 49 ].…”

“…Having an increased risk for hereditary BC implies being confronted with and challenged by uncertainty for a lifetime [ 22 , 47 , 48 ]. Studies even suggest that women who carry a pathogenic variant in an MBCG experience higher levels of uncertainty compared to carriers of a pathogenic variant in the high-risk genes BRCA1/2 [ 20 , 22 , 49 ]. This difference might be caused by the limited empirical data about cancer risk estimates and about the effectiveness of risk management strategies for MBCG.…”

“…According to Waltz et al [ 21 ], research on how to communicate risk and treatment decisions concerning BC genes beyond BRCA1/2 is crucial. Furthermore, studies focusing on high-risk pathogenic variants should not be extrapolated to those who carry moderate-risk pathogenic variants [ 20 , 22 ]. Reyes et al conducted a qualitative study with women carrying a CHEK2 or ATM pathogenic variant and focused on this very special experience of uncertainty regarding specific cancer risk estimates and regarding the effectiveness of certain risk management strategies [ 22 ].…”

“…Furthermore, studies focusing on high-risk pathogenic variants should not be extrapolated to those who carry moderate-risk pathogenic variants [ 20 , 22 ]. Reyes et al conducted a qualitative study with women carrying a CHEK2 or ATM pathogenic variant and focused on this very special experience of uncertainty regarding specific cancer risk estimates and regarding the effectiveness of certain risk management strategies [ 22 ]. Beyond this, to the authors’ knowledge, emerging feelings, coping styles, and support needs of women confronted with a pathogenic variant in a MBCG have not been assessed so far.…”