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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Upon request, the raw data supporting the conclusions of this article will be made available by the authors.
Coding of interview transcripts was facilitated by Dedoose (Version 8.2.14, 2019).
Idos GE, Kurian AW, Ricker C et al (2019) Multicenter prospective cohort study of the diagnostic yield and patient experience of multiplex gene panel testing for hereditary cancer risk. JCO Precis Oncol 3:1–19. https://doi.org/10.1200/PO.18.00217
Rainville IR, Rana HQ (2014) Next-generation sequencing for inherited breast cancer risk: counseling through the complexity. Curr Oncol Rep 16:371. https://doi.org/10.1007/s11912-013-0371-z
Bradbury AR, Patrick-Miller L, Long J et al (2015) Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility. Genet Med 17:485–492. https://doi.org/10.1038/gim.2014.134
Cybulski C, Wokołorczyk D, Jakubowska A et al (2011) Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29:3747–3752. https://doi.org/10.1200/JCO.2010.34.0778
Mavaddat N, Peock S, Frost D et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. JNCI J Natl Cancer Inst 105:812–822. https://doi.org/10.1093/jnci/djt095
Marabelli M, Cheng S-C, Parmigiani G (2016) Penetrance of ATM gene mutations in breast cancer: a meta-analysis of different measures of risk. Genet Epidemiol 40:425–431. https://doi.org/10.1002/gepi.21971
Catana A, Apostu AP, Antemie R-G (2019) Multi gene panel testing for hereditary breast cancer - is it ready to be used? Med Pharm Rep 92:220–225. https://doi.org/10.15386/mpr-1083
Cella D, Hughes C, Peterman A et al (2002) A brief assessment of concerns associated with genetic testing for cancer: the multidimensional impact of cancer risk assessment (MICRA) questionnaire. Health Psychol 21:564–572. https://doi.org/10.1037/0278-6184.108.40.2064
Hall MJ, Patrick-Miller LJ, Egleston BL et al (2018) Use and patient-reported outcomes of clinical multigene panel testing for cancer susceptibility in the multicenter communication of genetic test results by telephone study. JCO Precis Oncol 2:1–12. https://doi.org/10.1200/po.18.00199
Di Prospero LS, Seminsky M, Honeyford J et al (2001) Psychosocial issues following a positive result of genetic testing for BRCA1 and BRCA2 mutations: findings from a focus group and a needs-assessment survey. CMAJ Can Med Assoc J 164:1005–1009
Claes E, Evers-Kiebooms G, Denayer L et al (2005) Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure. J Genet Couns 14:349–363. https://doi.org/10.1007/s10897-005-1371-4
Oliveri S, Ferrari F, Manfrinati A, Pravettoni G (2018) A systematic review of the psychological implications of genetic testing: a comparative analysis among cardiovascular, neurodegenerative and cancer diseases. Front Genet 9:624. https://doi.org/10.3389/fgene.2018.00624
Esteban I, Vilaró M, Adrover E et al (2018) Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain. Psycho Oncol 27:1530–1537. https://doi.org/10.1002/pon.4686
Tung N, Domchek SM, Stadler Z et al (2016) Counselling framework for moderate-penetrance cancer-susceptibility mutations HHS Public Access. Nat Rev Clin Oncol 13:581–588. https://doi.org/10.1038/nrclinonc.2016.90
National Comprehensive Cancer Network (NCCN) (2020) Genetic/familial high-risk assessment: breast, ovarian, and pancreatic (version 1.2021). https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf. Accessed 15 Sep 2020
Kurian AW, Antoniou AC, Domchek SM (2016) Refining breast cancer risk stratification: additional genes, additional information. Am Soc Clin Oncol Educ Book 36:44–56. https://doi.org/10.1200/EDBK_158817
West AH, Blazer KR, Stoll J et al (2018) Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk. Fam Cancer 17:495–505. https://doi.org/10.1007/s10689-018-0070-x
Kurian AW, Hughes E, Handorf EA et al (2017) Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precis Oncol 1:1–12. https://doi.org/10.1200/PO.16.00066
Pilié PG, Johnson AM, Hanson K et al (2017) Germline genetic variants in men with prostate cancer and one or more additional cancers. Cancer 123:3925–3932. https://doi.org/10.1002/cncr.30817
Shindo K, Yu J, Suenaga M et al (2017) Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol 35:3382–3390. https://doi.org/10.1200/JCO.2017.72.3502
National Comprehensive Cancer Network (2020) Genetic/familial high-risk assessment: colorectal (Version 1.2020). https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Accessed 15 Sep 2020
Bartley N, Napier C, Best M, Butow P (2020) Patient experience of uncertainty in cancer genomics: a systematic review. Genet Med 22:1450–1460. https://doi.org/10.1038/s41436-020-0829-y
Han PKJ, Umstead KL, Bernhardt BA et al (2017) A taxonomy of medical uncertainties in clinical genome sequencing. Genet Med 19:918–925. https://doi.org/10.1038/gim.2016.212
Dean M (2016) “It’s not if I get cancer, it’s when I get cancer”: BRCA-positive patients’ (un)certain health experiences regarding hereditary breast and ovarian cancer risk. Soc Sci Med 163:21–27. https://doi.org/10.1016/j.socscimed.2016.06.039
Fisher CL, Roccotagliata T, Rising CJ et al (2017) “I don’t want to be an Ostrich”: managing mothers’ uncertainty during BRCA1/2 genetic counseling. J Genet Couns 26:455–468. https://doi.org/10.1007/s10897-016-9998-x
Rauscher EA, Dean M, Campbell-Salome GM (2018) “I am uncertain about what my uncertainty even is”: men’s uncertainty and information management of their BRCA-related cancer risks. J Genet Couns 27:1417–1427. https://doi.org/10.1007/s10897-018-0276-y
Vaismoradi M, Turunen H, Bondas T (2013) Content analysis and thematic analysis: implications for conducting a qualitative descriptive study. Nurs Health Sci 15:398–405. https://doi.org/10.1111/nhs.12048
Saunders B, Sim J, Kingstone T et al (2018) Saturation in qualitative research: exploring its conceptualization and operationalization. Qual Quant 52:1893–1907. https://doi.org/10.1007/s11135-017-0574-8
DeCuir-Gunby JT, Marshall PL, McCulloch AW (2011) Developing and using a codebook for the analysis of interview data: an example from a professional development research project. Field Methods 23:136–155. https://doi.org/10.1177/1525822X10388468
Barbour RS (2001) Education and debate Checklists for improving rigour in qualitative research: a case of the tail wagging the dog? BMJ 322:1115. https://doi.org/10.1136/bmj.322.7294.1115
Guest G, MacQueen KM (2008) Handbook for team-based qualitative research. Rowman Altamira
Campbell JL, Quincy C, Osserman J, Pedersen OK (2013) Coding in-depth semistructured interviews: problems of unitization and intercoder reliability and agreement. Sociol Methods Res 42:294–320. https://doi.org/10.1177/0049124113500475
Hughes C, Gomez-Caminero A, Benkendorf J et al (1997) Ethnic differences in knowledge and attitudes about BRCA1 testing in women at increased risk. Patient Educ Couns 32:51–62. https://doi.org/10.1016/S0738-3991(97)00064-5
Kessler L, Collier A, Brewster K et al (2005) Attitudes about genetic testing and genetic testing intentions in African American women at increased risk for hereditary breast cancer. Genet Med 7:230–238. https://doi.org/10.1097/01.GIM.0000159901.98315.FE
Scott D, Friedman S, Telli ML, Kurian AW (2020) Decision making about genetic testing among women with a personal and family history of breast cancer. JCO Oncol Pract 16:e37–e55. https://doi.org/10.1200/JOP.19.00221
Makhnoon S, Shirts BH, Bowen DJ (2019) Patients’ perspectives of variants of uncertain significance and strategies for uncertainty management. J Genet Couns 28:313–325. https://doi.org/10.1002/jgc4.1075
Medendorp NM, Hillen MA, Murugesu L et al (2019) Uncertainty related to multigene panel testing for cancer: a qualitative study on counsellors’ and counselees’ views. J Commun Genet 10:303–312. https://doi.org/10.1007/s12687-018-0393-1
Han PKJ, Reeve BB, Moser RP, Klein WMP (2009) Aversion to ambiguity regarding medical tests and treatments: measurement, prevalence, and relationship to sociodemographic factors. J Health Commun 14:556–572. https://doi.org/10.1080/10810730903089630
Yeh VM, Schnur JB, Margolies L, Montgomery GH (2015) Dense breast tissue notification: impact on women’s perceived risk, anxiety, and intentions for future breast cancer screening. J Am Coll Radiol JACR 12:261–266. https://doi.org/10.1016/j.jacr.2014.11.001
Jepson RG, Forbes CA, Sowden AJ, Lewis RA (2001) Increasing informed uptake and non-uptake of screening: evidence from a systematic review. Health Expect Int J Public Particip Health Care Health Policy 4:116–130. https://doi.org/10.1046/j.1369-6513.2001.00143.x
Volk RJ (2003) Patient education for informed decision making about prostate cancer screening: a randomized controlled trial with 1-year follow-up. Ann Fam Med 1:22–28. https://doi.org/10.1370/afm.7
Portnoy DB, Han PKJ, Ferrer RA et al (2013) Physicians’ attitudes about communicating and managing scientific uncertainty differ by perceived ambiguity aversion of their patients. Health Expect 16:362–372. https://doi.org/10.1111/j.1369-7625.2011.00717.x
Glassey R, O’Connor M, Ives A et al (2018) Heightened perception of breast cancer risk in young women at risk of familial breast cancer. Fam Cancer 17:15–22. https://doi.org/10.1007/s10689-017-0001-2
Scherr CL, Ramesh S, Getachew-Smith H et al (2020) How patients deal with an ambiguous medical test: decision-making after genetic testing. Patient Educ Couns. S0738-3991(20)30557-7. https://doi.org/10.1016/j.pec.2020.10.020
Waltz M, Prince AER, O’Daniel JM et al (2020) Referencing BRCA in hereditary cancer risk discussions: In search of an anchor in a sea of uncertainty. J Genet Couns 4:1219. https://doi.org/10.1002/jgc4.1219
Senay I, Kaphingst KA (2009) Anchoring-and-adjustment bias in communication of disease risk. Med Decis Making 29:193–201. https://doi.org/10.1177/0272989X08327395
Solomon I, Harrington E, Hooker G et al (2017) Lynch syndrome limbo: patient understanding of variants of uncertain significance. J Genet Couns 26:866–877. https://doi.org/10.1007/s10897-017-0066-y
Griffin CA, Axilbund JE, Codori AM et al (2007) Patient preferences regarding recontact by cancer genetics clinicians. Fam Cancer 6:265–273. https://doi.org/10.1007/s10689-007-9117-0
David KL, Brenman LM, Bush L et al (2019) Patient re-contact after revision of genomic test results: points to consider—a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 21:769–771. https://doi.org/10.1038/s41436-018-0391-z
Otten E, Plantinga M, Birnie E et al (2015) Is there a duty to recontact in light of new genetic technologies? A systematic review of the literature. Genet Med 17:668–678. https://doi.org/10.1038/gim.2014.173
Giesbertz NAA, van Harten WH, Bredenoord AL (2019) A duty to recontact in genetics: context matters. Nat Rev Genet 20:371–372. https://doi.org/10.1038/s41576-019-0121-7
Bensend TA, Veach PM, Niendorf KB (2014) What’s the harm? Genetic counselor perceptions of adverse effects of genetics service provision by non-genetics professionals. J Genet Couns 23:48–63. https://doi.org/10.1007/s10897-013-9605-3
Braun V, Clarke V (2013) Successful qualitative research: a practical guide for beginners. SAGE
Dean M, Campbell-Salome G, Rauscher EA (2020) Engaging men with brca-related cancer risks: practical advice for BRCA risk management from male stakeholders. Am J Mens Health 14:1557988320924932. https://doi.org/10.1177/1557988320924932
This study was completed in partial fulfillment of the requirements of the first author’s Master of Science degree in Human Genetics and Genetic Counseling from Stanford University’s School of Medicine. This work has been supported by the Jane Engelberg Memorial Fellowship Student Research Award, provided by the Engelberg Foundation to the National Society of Genetic Counselors, Inc. We wish to thank the participants of this study for providing their time and their thoughtful responses, and Janine Bruce and Sylvia Bereknyei Merrell for their qualitative methods guidance throughout the study.
This work was supported by the Jane Engelberg Memorial Fellowship Student Research Award, provided by the Engelberg Foundation to the National Society of Genetic Counselors, Inc.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Stanford University Institutional Review Board (09/18/2019; #51975).
Consent to participate
A waiver of written documentation of informed consent was granted, given the minimal risk of the study. Participants reviewed an information sheet prior to completing the demographic survey and provided verbal consent at the start of the interview.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Reyes, K.G., Clark, C., Gerhart, M. et al. “I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants. Familial Cancer (2021). https://doi.org/10.1007/s10689-021-00251-3
- Cancer genetics
- Genetic testing
- Qualitative research