Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities

Meghan J Walker^{1

2}, Kristina M Blackmore¹, Amy Chang¹, Laurence Lambert-Côté³, Annie Turgeon³, Antonis C Antoniou⁴, Kathleen A Bell¹, Mireille J M Broeders⁵, Jennifer D Brooks², Tim Carver⁴, Jocelyne Chiquette^{3

6}, Philippe Després⁷, Douglas F Easton⁴, Andrea Eisen^{1

8}, Laurence Eloy⁹, D Gareth Evans¹⁰, Samantha Fienberg¹, Yann Joly¹¹, Raymond H Kim^{1

12}, Shana J Kim², Bartha M Knoppers¹¹, Aisha K Lofters^{2

13}, Hermann Nabi^{3

14

15}, Jean-Sébastien Paquette⁶, Nora Pashayan^{4

16}, Amanda J Sheppard^{1

2}, Tracy L Stockley^{17

18}, Michel Dorval^{3

15

19}, Jacques Simard^{3

20}, Anna M Chiarelli^{1

2}

Affiliations

¹ Ontario Health (Cancer Care Ontario), Toronto, ON M5G 2L3, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada.
³ CHU de Québec-Université Laval Research Center, Queébec City, QC G1V 4G2, Canada.
⁴ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK.
⁵ Department for Health Evidence, Radboud University Medical Center, 6525EP Nijmegen, The Netherlands.
⁶ Department of Family Medicine and Emergency Medicine, Faculty of Medicine, Université Laval, Québec City, QC G1V 0A6, Canada.
⁷ Department of Physics, Engineering Physics and Optics, Faculty of Science and Engineering, Université Laval, Quebec City, QC G1V 0A6, Canada.
⁸ Sunnybrook Health Science Center, Toronto, ON M4N 3M5, Canada.
⁹ Québec Cancer Program, Ministère de la Santé et des Services Sociaux, Quebec City, QC G1S 2M1, Canada.
¹⁰ Division of Evolution Infection and Genomic Sciences, The University of Manchester, Manchester M13 9PL, UK.
¹¹ Centre of Genomics and Policy, McGill University, Montreal, QC H3A 0G1, Canada.
¹² Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
¹³ Women's College Research Institute, Toronto, ON M5G 1N8, Canada.
¹⁴ Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada.
¹⁵ Université Laval Cancer Research Center, Quebec City, QC G1R 3S3, Canada.
¹⁶ Department of Applied Health Research, Institute of Epidemiology and Healthcare, University College London, London WC1E 6BT, UK.
¹⁷ Division of Clinical Laboratory Genetics, University Health Network, Toronto, ON M5G 2C4, Canada.
¹⁸ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
¹⁹ Faculty of Pharmacy, Université Laval, Quebec City, QC G1V 0A6, Canada.
²⁰ Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 4G2, Canada.

PMID: 38893236
PMCID: PMC11171515
DOI: 10.3390/cancers16112116

Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities

Meghan J Walker et al. Cancers (Basel). 2024.

. 2024 May 31;16(11):2116.

doi: 10.3390/cancers16112116.

Authors

Affiliations

¹ Ontario Health (Cancer Care Ontario), Toronto, ON M5G 2L3, Canada.
² Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5S 1A1, Canada.
³ CHU de Québec-Université Laval Research Center, Queébec City, QC G1V 4G2, Canada.
⁴ Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge CB1 8RN, UK.
⁵ Department for Health Evidence, Radboud University Medical Center, 6525EP Nijmegen, The Netherlands.
⁶ Department of Family Medicine and Emergency Medicine, Faculty of Medicine, Université Laval, Québec City, QC G1V 0A6, Canada.
⁷ Department of Physics, Engineering Physics and Optics, Faculty of Science and Engineering, Université Laval, Quebec City, QC G1V 0A6, Canada.
⁸ Sunnybrook Health Science Center, Toronto, ON M4N 3M5, Canada.
⁹ Québec Cancer Program, Ministère de la Santé et des Services Sociaux, Quebec City, QC G1S 2M1, Canada.
¹⁰ Division of Evolution Infection and Genomic Sciences, The University of Manchester, Manchester M13 9PL, UK.
¹¹ Centre of Genomics and Policy, McGill University, Montreal, QC H3A 0G1, Canada.
¹² Princess Margaret Cancer Centre, Toronto, ON M5G 2M9, Canada.
¹³ Women's College Research Institute, Toronto, ON M5G 1N8, Canada.
¹⁴ Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada.
¹⁵ Université Laval Cancer Research Center, Quebec City, QC G1R 3S3, Canada.
¹⁶ Department of Applied Health Research, Institute of Epidemiology and Healthcare, University College London, London WC1E 6BT, UK.
¹⁷ Division of Clinical Laboratory Genetics, University Health Network, Toronto, ON M5G 2C4, Canada.
¹⁸ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
¹⁹ Faculty of Pharmacy, Université Laval, Quebec City, QC G1V 0A6, Canada.
²⁰ Department of Molecular Medicine, Faculty of Medicine, Université Laval, Quebec City, QC G1V 4G2, Canada.

PMID: 38893236
PMCID: PMC11171515
DOI: 10.3390/cancers16112116

Abstract

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

Keywords: breast cancer; breast cancer screening; implementation; polygenic risk score; risk assessment; risk stratification.

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Conflict of interest statement

Antonis C. Antoniou, Tim Carver and Douglas F. Easton are creators of BOADICEA, which has been licensed to Cambridge Enterprise (University of Cambridge). The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. All other authors declare no conflicts of interest.

Figures

**Figure 1**
Recruitment and data collection of Quebec and Ontario PERSPECTIVE I&I participants aged 40–69 years. Abbreviations: polygenic risk score (PRS). * Risk estimated without PRS for n = 3.

See this image and copyright information in PMC

References

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Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities

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Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities

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Conflict of interest statement

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