"I don't need any more unknowns hanging over my head": Views of patients with cancer on variants of uncertain significance and low/moderate risk results from genomic sequencing

Salma Shickh; Chloe Mighton; Marc Clausen; Rita Kodida; Ella Adi-Wauran; Daena Hirjikaka; Suvetha Krishnapillai; Emma Reble; Jordan Sam; Nancy N Baxter; Andreas Laupacis; Yvonne Bombard; Incidental Genomics Study Team

doi:10.1016/j.gim.2023.100960

"I don't need any more unknowns hanging over my head": Views of patients with cancer on variants of uncertain significance and low/moderate risk results from genomic sequencing

Genet Med. 2023 Dec;25(12):100960. doi: 10.1016/j.gim.2023.100960. Epub 2023 Aug 11.

Collaborators

Incidental Genomics Study Team:
Yvonne Bombard⁶, Susan Randall Armel⁷, Melyssa Aronson⁸, Nancy N Baxter³, Kenneth Bond⁹, José-Mario Capo-Chichi¹⁰, June C Carroll¹¹, Timothy Caulfield¹², Marc Clausen², Tammy J Clifford¹³, Iris Cohn¹⁴, Irfan Dhalla¹⁵, Craig C Earle¹⁶, Andrea Eisen¹⁷, Christine Elser⁸, Michael Evans¹⁸, Emily Glogowski¹⁹, Tracy Graham²⁰, Elena Greenfeld²¹, Jada G Hamilton²², Wanrudee Isaranuwatchai⁴, Monika Kastner²³, Raymond H Kim²⁴, Andreas Laupacis⁴, Jordan Lerner-Ellis²⁵, Chantal F Morel²⁶, Michelle Mujoomdar²⁷, Abdul Noor²¹, Kenneth Offit²², Seema Panchal⁸, Mark E Robson²², Stephen W Scherer²⁸, Adena Scheer²⁹, Kasmintan A Schrader³⁰, Terrence Sullivan³¹, Kevin E Thorpe³²

Affiliations

¹ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
² Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³ Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Surgery, University of Toronto, Toronto, ON, Canada; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.
⁴ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada. Electronic address: [email protected].
⁶ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; Genomics Health Services Research Program, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, ON, Canada.
⁷ Princess Margaret Cancer Centre, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada.
⁸ University of Toronto, Toronto, ON, Canada; Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
⁹ Institute of Health Economics, Edmonton, AB, Canada.
¹⁰ University Health Network, Toronto, ON, Canada.
¹¹ Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
¹² Faculty of Law, University of Alberta, Edmonton, AB, Canada; School of Public Health, University of Alberta, Edmonton, AB, Canada; Health Law Institute, University of Alberta, Edmonton, AB, Canada.
¹³ School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
¹⁴ The Hospital for Sick Children, Toronto, ON, Canada.
¹⁵ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada; Institute for Clinical Evaluative Sciences, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁷ Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁸ St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
¹⁹ Sanofi Genzyme, New York, NY.
²⁰ University of Toronto, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²¹ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Division of Diagnostic Medical Genetics, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
²² Memorial Sloan Kettering Cancer Center, New York, NY.
²³ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada.
²⁴ University of Toronto, Toronto, ON, Canada; Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; The Hospital for Sick Children, Toronto, ON, Canada.
²⁵ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON Canada; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.
²⁶ Mount Sinai Hospital, Sinai Health, Toronto, ON, Canada.
²⁷ Canadian Agency for Drugs and Technologies in Health, Ottawa, ON, Canada.
²⁸ The Hospital for Sick Children, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada; Division of Diagnostic Medical Genetics, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
²⁹ Department of Surgery, University of Toronto, Toronto, ON, Canada; St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³⁰ BC Cancer, Vancouver, BC, Canada; The University of British Columbia, Vancouver, BC, Canada.
³¹ Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
³² Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.

Abstract

Purpose: We sought to explore patient-reported utility of all types of cancer results from genomic sequencing (GS).

Methods: Qualitative study, using semi-structured interviews with patients who underwent GS within a trial. Thematic analysis employing constant comparison was used. Two coders coded transcripts, with use of a third coder to resolve conflicts.

Results: 25 patients participated: female (22), >50 years (18), European (12), Ashkenazi Jewish (5), Middle Eastern (3), or other ethnicity (5), with breast cancer history (20). Patients' perceptions of the utility of cancer GS results hinged on whether they triggered clinical action. For example, when patients were enrolled into high-risk breast cancer surveillance programs for low/moderate risk breast cancer genes, they perceived the results to be very "useful" and of moderate-high utility. In contrast, patients receiving low/moderate risk or primary variants of uncertain significance results without clinical action perceived results as "concerning," leading to harms, such as hypervigilance about cancer symptoms. Overall, having supportive relatives or providers enhanced perceptions of utility.

Conclusion: Patients' perceptions of cancer GS results hinged on whether they triggered clinical management. Consequently, patients who received results without clinical action became hypervigilant, experiencing harms. Our findings call for a need to develop practice interventions to support patients with cancer undergoing GS.

Keywords: Clinical utility; Genomic sequencing; Health services research; Hereditary cancer syndromes; Patient-reported utility.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / genetics
Clinical Trials as Topic
Confidentiality
Female
Genomics
Humans
Male
Middle Aged
Qualitative Research

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States