Advertisement

Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals

Published:September 03, 2022DOI:https://doi.org/10.1016/j.gim.2022.08.001

      ABSTRACT

      Purpose

      Health care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals’ (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development.

      Methods

      A cross-sectional survey was conducted using a bilingual—English/French—online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021.

      Results

      A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities.

      Conclusion

      The study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.

      Keywords

      Introduction

      Breast cancer (BC) remains the most common cancer diagnosed among women worldwide.
      • Sung H.
      • Ferlay J.
      • Siegel R.L.
      • et al.
      Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
      There is compelling evidence suggesting that early detection of BC significantly reduces mortality from the disease,
      • Dibden A.
      • Offman J.
      • Duffy S.W.
      • Gabe R.
      Worldwide review and meta-analysis of cohort studies measuring the effect of mammography screening programmes on incidence-based breast cancer mortality.
      but this comes with risks of false positive screening results, overdiagnosis, and psychological effects.
      • Lauby-Secretan B.
      • Scoccianti C.
      • Loomis D.
      • et al.
      Breast-cancer screening—viewpoint of the IARC Working Group.
      Emerging evidence suggest that a risk-stratified approach to BC screening can improve its benefit to risk ratio by targeting those women most likely to benefit from it, potentially leading to reduced BC-specific mortality as well as allowing for more efficient allocation of health care resources.
      • van den Broek J.J.
      • Schechter C.B.
      • van Ravesteyn N.T.
      • et al.
      Personalizing breast cancer screening based on polygenic risk and family history.
      This stratification approach, currently under investigation in Canada,
      • Brooks J.D.
      • Nabi H.H.
      • Andrulis I.L.
      • et al.
      Personalized risk assessment for prevention and early detection of breast cancer: integration and implementation (PERSPECTIVE I&I).
      the United States,
      • Esserman L.J.
      • Investigators Athena
      WISDOM Study
      The WISDOM Study: breaking the deadlock in the breast cancer screening debate.
      and Europe,
      Horizon 2020
      MyPeBS Personalising Breast Screening. MyPeBS.
      encompasses 3 steps: first, collection of women’s personal and genetic information; second, calculation of their risk of developing BC within a given time horizon using a risk prediction model; and third, disclosure of the risk level and the possible screening and risk reduction actions to participants. Several BC risk prediction models are now incorporating a polygenic risk score (PRS).
      • Zhang X.
      • Rice M.
      • Tworoger S.S.
      • et al.
      Addition of a polygenic risk score, mammographic density, and endogenous hormones to existing breast cancer risk prediction models: A nested case-control study.
      The PRS—derived from genome-wide associations studies—is a score that combines the effects of several common genetic variants with small individual effect sizes but when combined are strongly associated with the risk of developing the medical condition.
      • Mavaddat N.
      • Michailidou K.
      • Dennis J.
      • et al.
      Polygenic risk scores for prediction of breast cancer and breast cancer subtypes.
      The integration of risk-stratified BC screening into health systems will require health care professionals (HCPs) to show new competencies in terms of knowledge, skills, and attitudes.
      • Chowdhury S.
      • Henneman L.
      • Dent T.
      • et al.
      Do health professionals need additional competencies for stratified cancer prevention based on genetic risk profiling?.
      For example, primary care professionals and those from medical specialties other than genetics could be expected to explain both the harms and benefits of risk-stratified BC screening, interpret and communicate to patients their risk level obtained through a risk prediction model, and advise them on screening and preventive strategies.
      • Chowdhury S.
      • Henneman L.
      • Dent T.
      • et al.
      Do health professionals need additional competencies for stratified cancer prevention based on genetic risk profiling?.
      ,
      • Kirk M.
      • Calzone K.
      • Arimori N.
      • Tonkin E.
      Genetics-genomics competencies and nursing regulation.
      Some of the information to be exchanged through this process is complex. An example is the explanation of the calculation of the PRS, which requires a good level of familiarity, and ideally knowledge, for its responsible integration to clinical practice.
      Polygenic Risk Score Task Force of the International Common Disease Alliance
      Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps.
      However, little is known regarding HCPs’ familiarity with the concept of PRS and their perspectives regarding risk-stratified BC screening. Two small-size studies surveyed HCPs’ familiarity and use of PRS,
      • McGuinness M.
      • Fassi E.
      • Wang C.
      • Hacking C.
      • Ellis V.
      Breast cancer polygenic risk scores in the clinical cancer genetic counseling setting: current practices and impact on patient management.
      ,
      • Smit A.K.
      • Sharman A.R.
      • Espinoza D.
      • et al.
      Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: a cross-sectional survey of health professionals.
      but >84% of the participants were genetic counselors. Although genetic counselors are an important professional group to consider for the dissemination and implementation of risk-stratified screening approach, other HCPs, such as those involved in primary care, also need to be considered. In addition, investigation efforts to collect Canadian HCPs’ perspectives regarding risk-stratified BC screening have so far been mainly conducted through qualitative methodologies.
      • Esquivel-Sada D.
      • Lévesque E.
      • Hagan J.
      • Knoppers B.M.
      • Simard J.
      Envisioning implementation of a personalized approach in breast cancer screening programs: stakeholder perspectives.
      ,
      • Puzhko S.
      • Gagnon J.
      • Simard J.
      • Knoppers B.M.
      • Siedlikowski S.
      • Bartlett G.
      Health professionals’ perspectives on breast cancer risk stratification: understanding evaluation of risk versus screening for disease.
      A quantitative survey on a larger sample of HCPs from different medical specialties is thus needed to appraise the level of training required to support optimal implementation in the health care system.
      Canada has a universal health care system, known as Medicare, that emphasizes public administration, comprehensiveness, universality, portability, and accessibility (Canada Health Act).
      • Bégin M.
      Medicare: Canada’s right to health.
      Data from the Canadian Institute for Health Information (CIHI) estimated that the Canadian Medicare provides coverage for approximately 70% of Canadians’ health care needs, and the remaining 30% are covered by the private sector.
      Canadian Institute for Health Information
      Exploring the 70/30 Split: How Canadaís Health Care System Is Financed.
      There is no one centrally managed Canadian health care system, meaning that each of its jurisdictions (ie, 10 provinces and 3 territories) determine what medical acts are covered within their health care plan.
      • Government of Canada
      Health care in Canada: Access our universal health care system. Government of Canada. Accessed June 8, 2022.
      With the exception of 1 territory, all jurisdictions also implemented an organized public health program that includes offering regular BC screening mammograms.

      Public Health Agency of Canada. Organized breast cancer screening programs in Canada. Report on program performance in 2005 and 2006. Published 2011. Accessed June 8, 2022. https://www.canada.ca/content/dam/phac-aspc/migration/phac-aspc/cd-mc/publications/cancer/obcsp-podcs05/pdf/breast-cancer-report-eng.pdf

      Some provinces, such as Ontario and British Columbia, also have high-risk programs offering genetics counseling, testing, and/or enhanced screening strategies to women at increased risk.
      • Blood K.A.
      • McCullum M.
      • Wilson C.
      • Cheifetz R.E.
      Hereditary breast cancer in British Columbia: outcomes from BC Cancer’s High-Risk Clinic.
      , In all instances, HCPs in the primary care settings (nurses practitioners and family physicians alike) are advised to routinely adress BC screening practices with their patients.

      Canadian Task Force on Preventive Health Care. Breast cancer—clinician mammography recommendation. Published 2019. Accessed June 8, 2022. https://canadiantaskforce.ca/breast-cancer-clinician-mammography-recommendation/

      The most common types of health care setting for the prevention and treatment of BC include the hospital (academic when there is a University affiliation with research and training activities or community otherwise); the family health team, group, or network; the community health center; and the private clinic.

      Government of Canada. Canada’s health care system. Government of Canada. Published 2019. Accessed July 20, 2022. https://www.canada.ca/en/health-canada/services/health-care-system/reports-publications/health-care-system/canada.html#a11

      The later 3 settings do offer primary care services, but they do differ greatly in terms of registration and payment process.

      Government of Canada. Canada’s health care system. Government of Canada. Published 2019. Accessed July 20, 2022. https://www.canada.ca/en/health-canada/services/health-care-system/reports-publications/health-care-system/canada.html#a11

      For instance, patients would need to be registered within a family health team to have access to services, whereas unregistered patients could usually consult in a community health center or a private clinic. Private clinics are likely to charge for all services offered, whereas the family health teams and community health centers follow the provincial health care plan.
      This study aimed to explore HCPs’ (1) self-reported familiarity with the concept of PRS, (2) perceived level of knowledge regarding risk-stratified BC screening, and (3) preferences for continuing professional development (CPD). Evidence generated by this study provide crucial information about current professionals’ appraisal of their knowledge. This will support the design of CPD aiming to develop competency in supporting patients by understanding their BC risk level, making informed decisions related to screening and preventive interventions, and potentially avoiding unnecessary adverse psychosocial effects.

      Materials and Methods

      This study is part of PERSPECTIVE I&I (personalized risk assessment for prevention and early detection of breast cancer: integration and implementation), a major Canadian initiative assessing the feasibility and acceptability of implementing a risk-stratified BC screening approach.
      • Brooks J.D.
      • Nabi H.H.
      • Andrulis I.L.
      • et al.
      Personalized risk assessment for prevention and early detection of breast cancer: integration and implementation (PERSPECTIVE I&I).

      Study design and participants

      A cross-sectional study was conducted using an anonymous self-administrated online questionnaire targeting all HCPs interested in providing their opinions, attitudes, and expectations regarding risk-stratified BC screening. Although there were no inclusion/exclusion criteria for participants, our promotion and diffusion strategy targeted physicians and nurses from all medical specialties. The study invitation with the link to the questionnaire was disseminated between November 2020 and May 2021 through several professional associations and health care institutions’ newsletters and communication platforms across Canada (see Supplemental Tables 1–3) as well as through PERSPECTIVE I&I coinvestigators’ networks. The first page of our questionnaire provided elements of context about the study and informed participants that consent was implied by the voluntary completion of the questionnaire. The CHU de Québec-Université Laval’s Institutional Review Board approved this study (registration number: F9-55772).

      Questionnaire development

      The questionnaire was developed in French and English by a multidisciplinary team of clinicians, epidemiologists, and social scientists after reviewing the relevant literature.
      • Esquivel-Sada D.
      • Lévesque E.
      • Hagan J.
      • Knoppers B.M.
      • Simard J.
      Envisioning implementation of a personalized approach in breast cancer screening programs: stakeholder perspectives.
      ,
      • Puzhko S.
      • Gagnon J.
      • Simard J.
      • Knoppers B.M.
      • Siedlikowski S.
      • Bartlett G.
      Health professionals’ perspectives on breast cancer risk stratification: understanding evaluation of risk versus screening for disease.
      ,

      Gagnon J, Lévesque E, Clinical Advisory Committee on Breast Cancer Screening and Prevention, et al. Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies. Curr Oncol. 2016;23(6):e615–e625. http://doi.org/10.1093/jnci/djw290

      • Shieh Y.
      • Eklund M.
      • Madlensky L.
      • et al.
      Breast cancer screening in the precision medicine era: risk-based screening in a population-based trial.
      • Koitsalu M.
      • Sprangers M.A.
      • Eklund M.
      • et al.
      Public interest in and acceptability of the prospect of risk-stratified screening for breast and prostate cancer.
      The questionnaire had a total of 17 questions, with data from 10 questions analyzed to achieve our 3 objectives (see Supplemental Questionnaire/Supplemental Methods). After a short preamble explaining the risk-based BC screening approach, questions covered familiarity with the concept of PRS (1 question); opinions regarding their level of knowledge; the status of their training and the future professional curriculum on risk assessment, including genetic factors (1 question comprising 5 statements); preferences for continuing professional education (3 questions); and sociodemographic and professional status (5 questions). The French and English questionnaires were pilot-tested within the network of physicians collaborating on the study and comments were addressed by the research team. The Research Electronic Data Capture platform was used for the questionnaire web-based interface.
      • Harris P.A.
      • Taylor R.
      • Thielke R.
      • Payne J.
      • Gonzalez N.
      • Conde J.G.
      Research Electronic Data Capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support.

      Statistical analyses

      The 5-point Likert scale of the question assessing participants’ level of familiarity with the concept of PRS was categorized on 3 levels: “Very familiar and familiar,” “Very unfamiliar and unfamiliar,” and “Don’t know this concept.” HCPs were categorized as “Physician,” “Nurse,” or “Other.” Medical specialties were categorized as “Family medicine/Primary care,” “Oncology,” and “Other.” The number of years of experience was categorized as follow: <5 years, between 5 and 14 years, between 15 and 25 years, and >25 years. The region of practice was categorized as “Province of Québec,” “Province of Ontario,” and “Other Canadian provinces and territories.”
      Descriptive statistics were used to summarize participant responses. χ2 tests were used to explore whether participants’ level of familiarity with the concept of PRS differed according to sociodemographic and professional status variables. Dummy variables were created for missing responses. Analyses using listwise deletion of missing variables were also conducted as a sensitivity analysis.
      • Enders C.K.
      Applied Missing Data Analysis.
      All tests were 2-sided with a 0.05 level of significance. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute Inc).

      Results

      A total of 593 HCPs opened the survey link and completed more than 2 questions. A total of 453 participants responded to all questions. Overall, 432 (93.5%) participants were female, 103 (22.3%) were physicians, and 323 (69.7%) were nurses (ie, nurses and nurse practitioners) (Table 1). The distribution by specialty was as follows: family medicine/primary care (36.1%), oncology (12.8%), and other (51.1%). Other medical specialties included: internal medicine, surgery, emergency, palliative care, public health medicine, radiology, and obstetrics-gynecology. The province of Québec was the most frequent region of practice for participants (82.9%), followed by Ontario (10.1%), and other Canadian provinces and territories (7.0%). Participants’ most frequent practice settings included academic hospital (28.9%), community hospital (21.3%), community health center (17%), and family health team, group, or network (16.3%). Finally, more than 89% of participants agreed or strongly agreed that BC screening is an effective method for early detection of BC.
      Table 1Participants’ characteristics (N = 593)
      Sociodemographic and Professional StatusFrequency, n (%)
      Gender
       Women432 (93.5)
       Men30 (6.5)
       Missing data/prefer not to answer131
      Profession
       Physician103 (22.3)
       Nurse323 (69.7)
       Other
      Other professions included genetic counselor, physiotherapist, occupational therapist, radiologist, researcher, and technologist.
      37 (8.0)
       Missing data130
      Medical specialty
       Family medicine/primary care167 (36.1)
       Oncology59 (12.8)
       Other
      Other medical specialties included internal medicine, surgery, emergency, palliative care, public health medicine, radiology, and obstetrics-gynecology.
      236 (51.1)
       Missing data131
      Number of years of practice
       <5 years58 (12.5)
       5-14 years135 (29.2)
       15-25 years113 (24.4)
       >25 years157 (33.9)
       Missing data130
      Region of practice
       Province of Québec377 (82.9)
       Province of Ontario46 (10.1)
       Other provinces32 (7.0)
       Missing data138
      Practice setting
       Academic hospital133 (28.9)
       Community hospital98 (21.3)
       Family health team/group/network75 (16.3)
       Community health center78 (17.0)
       Private clinic25 (5.4)
       Other
      Other practice settings included intensive care unit, nurse practitioner-led clinic, nursing home, public health agency, and research center.
      51 (11.1)
       Missing data133
      Level of agreement with the statement, “breast cancer screening is an effective method for early detection of breast cancer”
       Agree or strongly agree528 (89.3)
       Neither agree nor disagree25 (4.2)
       Disagree or strongly disagree31 (5.3)
       Don’t know7 (1.2)
       Missing data2
      a Other professions included genetic counselor, physiotherapist, occupational therapist, radiologist, researcher, and technologist.
      b Other medical specialties included internal medicine, surgery, emergency, palliative care, public health medicine, radiology, and obstetrics-gynecology.
      c Other practice settings included intensive care unit, nurse practitioner-led clinic, nursing home, public health agency, and research center.
      The vast majority of participants reported to be unfamiliar (19.9%), very unfamiliar (31.9%) with or did not know (40.5%) the concept of PRS (Figure 1). Exploratory univariate analyses revealed that the profession, medical specialty, and region of practice were associated with a different report of familiarity with the concept of PRS, with doctors being more familiar with the concept than other professions, oncologists reporting more familiarity than other medical specialties, and people from the province of Québec reporting less familiarity with the concept of PRS. Gender, number of years of practice, and practice setting were not associated with familiarity with the concept of PRS (Figure 2 and Supplemental Tables 1–3). Similar pattern of associations were observed when missing data were excluded.
      Figure thumbnail gr1
      Figure 1Participants’ level of familiarity with the concept of polygenic risk score (N = 593).
      Figure thumbnail gr2
      Figure 2Association between familiarity with the concept of polygenic risk score and sociodemographic variables (N = 593).
      When asked about their opinion regarding their level of knowledge toward risk-stratified BC screening and the ideal future professional curriculum on risk assessment, including genetic factors, the vast majority of participants answered that (1) they do not have enough knowledge (60.5%), (2) they would require more training (76.9%), and (3) the ideal medical and nursing curriculum should include more on this topic (70.3% and 71.3%, respectively) (Figure 3). However, only 45.9% answered that they would have time to educate themselves on risk-stratified BC screening.
      Figure thumbnail gr3
      Figure 3Participants’ perspective regarding their education and continuous professional development (N = 593).
      Figure 4 presents the preferred CPD resources, dissemination modalities, and topics to include in educational resources. Higher participant preference was observed for online training specific to risk-stratified BC screening (26%), with topics addressing the basics of risk-stratified BC screening (16%) and its interpretation (15%). Participants were less interested in general information on genetics and the ethical, legal, and social challenges of risk-stratified BC screening.
      Figure thumbnail gr4
      Figure 4Participants’ preferred (A) resources for general questions related to practice, (B) formats to learn more about risk-based breast cancer screening, and (C) topics to be included in resource material (participants were invited to check all that apply). BC, breast cancer; SNV, single nucleotide variation.

      Discussion

      This study provides important information on familiarity with the concept of PRS, perceived level of knowledge regarding risk-stratified BC screening, and preferences for CPD of HCPs not trained in genetics. Overall, HCPs reported low level of familiarity with the concept of PRS and limited knowledge regarding risk-stratified BC screening. The vast majority acknowledged their needs for CPD on these topics and that they would favor resources delivered online.
      To our knowledge, only 2 small-size studies (ie, sample sizes of 105
      • Smit A.K.
      • Sharman A.R.
      • Espinoza D.
      • et al.
      Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: a cross-sectional survey of health professionals.
      and 120
      • McGuinness M.
      • Fassi E.
      • Wang C.
      • Hacking C.
      • Ellis V.
      Breast cancer polygenic risk scores in the clinical cancer genetic counseling setting: current practices and impact on patient management.
      ) have reported HCPs’ level of familiarity with the concept of PRS. However, both studies were focused primarily on genetic counselors. Thus, the results of these studies are not comparable with ours because our study population was composed mainly of professionals not trained in genetics. Our study complements the evidence generated by these previous studies by providing the perspectives of a diverse group of HCPs and by highlighting the fact that, unlike genetic counselors, professionals not trained in genetics currently report a low level of familiarity with the concept of PRS. Having basic knowledge regarding the calculation and implications of a PRS is important for several HCPs, including front line professionals, such as nurses and primary care physicians. Indeed, if calculations of PRS are implemented in clinical practice, they would need to answer questions related to PRS results and support their patients in their decision process regarding appropriate screening recommendations and preventive options.
      • Chowdhury S.
      • Henneman L.
      • Dent T.
      • et al.
      Do health professionals need additional competencies for stratified cancer prevention based on genetic risk profiling?.
      ,
      Polygenic Risk Score Task Force of the International Common Disease Alliance
      Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps.
      HCPs should also be knowledgeable of the potential limitations of PRS and be able to convey a balanced message to their patients.
      • Marcon A.R.
      • Bieber M.
      • Caulfield T.
      Representing a “revolution”: how the popular press has portrayed personalized medicine.
      Finally, according to different possible implementation scenarios, front line HCPs may have an important role in identifying and referring individuals for whom a risk assessment that include a PRS calculation is most indicated.
      • Esquivel-Sada D.
      • Lévesque E.
      • Hagan J.
      • Knoppers B.M.
      • Simard J.
      Envisioning implementation of a personalized approach in breast cancer screening programs: stakeholder perspectives.
      ,
      • Knoppers B.M.
      • Bernier A.
      • Granados Moreno P.
      • Pashayan N.
      Of screening, stratification, and scores.
      The observation that the vast majority of our participants stated that they do not have enough knowledge about risk-stratified BC screening and would require more training is in line with several studies reporting that HCPs feel unprepared and lack the appropriate knowledge to competently integrate emerging genomic information into their practice.
      • Smit A.K.
      • Sharman A.R.
      • Espinoza D.
      • et al.
      Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: a cross-sectional survey of health professionals.
      • Esquivel-Sada D.
      • Lévesque E.
      • Hagan J.
      • Knoppers B.M.
      • Simard J.
      Envisioning implementation of a personalized approach in breast cancer screening programs: stakeholder perspectives.
      • Puzhko S.
      • Gagnon J.
      • Simard J.
      • Knoppers B.M.
      • Siedlikowski S.
      • Bartlett G.
      Health professionals’ perspectives on breast cancer risk stratification: understanding evaluation of risk versus screening for disease.
      ,
      • McCauley M.P.
      • Marcus R.K.
      • Strong K.A.
      • Visotcky A.M.
      • Shimoyama M.E.
      • Derse A.R.
      Genetics and genomics in clinical practice: the views of Wisconsin physicians.
      • Marzuillo C.
      • De Vito C.
      • D’Addario M.
      • et al.
      Are public health professionals prepared for public health genomics? A cross-sectional survey in Italy.
      • Paul J.L.
      • Leslie H.
      • Trainer A.H.
      • Gaff C.
      A theory-informed systematic review of clinicians’ genetic testing practices.
      • Owusu Obeng A.
      • Fei K.
      • Levy K.D.
      • et al.
      Physician-reported benefits and barriers to clinical implementation of genomic medicine: a multi-site IGNITE-network survey.
      Scientific literature about the concept of PRS and risk-stratified BC screening has been published since at least 2015.
      • Mavaddat N.
      • Pharoah P.D.
      • Michailidou K.
      • et al.
      Prediction of breast cancer risk based on profiling with common genetic variants.
      ,
      • Pashayan N.
      • Duffy S.W.
      • Neal D.E.
      • et al.
      Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis.
      Thus, reported low level of familiarity and knowledge of HCPs about these 2 aspects suggests that active dissemination strategies are required.
      To ensure a successful integration of the PRS and risk-stratified screening approaches, a comprehensive portfolio of CPD activities—adapted to the different professional groups and medical specialties—is necessary. Academic institutions will probably need to adapt their curriculum to address these knowledge gaps, and authoritative associations should be called upon to provide point-of-care resources, clinical guidelines, and implementation protocols for the responsible use of PRS information and sound implementation of risk-stratified BC screening.
      Polygenic Risk Score Task Force of the International Common Disease Alliance
      Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps.
      Although these analyses were exploratory, it is interesting to note that significant differences were observed on the level of familiarity with the concept of PRS according to participants’ profession, medical specialty, and region of practice. Previous studies assessing level of knowledge with genetics and/or genomics have reported similar differences across professions,
      • Marzuillo C.
      • De Vito C.
      • D’Addario M.
      • et al.
      Are public health professionals prepared for public health genomics? A cross-sectional survey in Italy.
      ,
      • Rahma A.T.
      • Elsheik M.
      • Ali B.R.
      • et al.
      Knowledge, attitudes, and perceived barriers toward genetic testing and pharmacogenomics among healthcare workers in the United Arab Emirates: a cross-sectional study.
      ,
      • Lopes-Júnior L.C.
      • Carvalho Júnior P.M.
      • de Faria Ferraz V.E.
      • Nascimento L.C.
      • Van Riper M.
      • Flória-Santos M.
      Genetic education, knowledge and experiences between nurses and physicians in primary care in Brazil: a cross-sectional study.
      medical specialties,
      • McCauley M.P.
      • Marcus R.K.
      • Strong K.A.
      • Visotcky A.M.
      • Shimoyama M.E.
      • Derse A.R.
      Genetics and genomics in clinical practice: the views of Wisconsin physicians.
      ,
      • Ha V.T.D.
      • Frizzo-Barker J.
      • Chow-White P.
      Adopting clinical genomics: a systematic review of genomic literacy among physicians in cancer care.
      ,
      • Hann K.E.J.
      • Fraser L.
      • Side L.
      • et al.
      Health care professionals’ attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.
      and geographic locations.
      • Ha V.T.D.
      • Frizzo-Barker J.
      • Chow-White P.
      Adopting clinical genomics: a systematic review of genomic literacy among physicians in cancer care.
      ,
      • Chow-White P.
      • Ha D.
      • Laskin J.
      Knowledge, attitudes, and values among physicians working with clinical genomics: a survey of medical oncologists.
      ,
      • Harding B.
      • Webber C.
      • Ruhland L.
      • et al.
      Primary care providers’ lived experiences of genetics in practice.
      These differences on the level of familiarity with the concept of PRS are probably partly explained by the type of services professionals are offering as well as their exposure to genetic services within their health care institutions.
      • Ha V.T.D.
      • Frizzo-Barker J.
      • Chow-White P.
      Adopting clinical genomics: a systematic review of genomic literacy among physicians in cancer care.
      For instance, in 2011, the province of Ontario, Canada, implemented its High Risk Ontario Breast Screening Program. The sole presence of such program may increase HCPs’ awareness related to genetics and genomics risk of BC. Uncovering the effect of professional and practice setting characteristics on the familiarity and knowledge about the concept of PRS and risk-stratified BC screening should be explored further through a more comprehensive assessment among different HCPs. This could serve as a parameter of guidance for the development of tailored CPD activities and resources.
      Our participants’ preference for online CPD resources is in line with other studies,
      • Smit A.K.
      • Sharman A.R.
      • Espinoza D.
      • et al.
      Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: a cross-sectional survey of health professionals.
      ,
      • McCauley M.P.
      • Marcus R.K.
      • Strong K.A.
      • Visotcky A.M.
      • Shimoyama M.E.
      • Derse A.R.
      Genetics and genomics in clinical practice: the views of Wisconsin physicians.
      ,
      • Carroll J.C.
      • Allanson J.
      • Morrison S.
      • et al.
      Informing integration of genomic medicine into primary care: an assessment of current practice, attitudes, and desired resources.
      although the in-person CPD modality was preferred in one.
      • Nisselle A.
      • King E.A.
      • McClaren B.
      • et al.
      Measuring physician practice, preparedness and preferences for genomic medicine: a national survey.
      We may hypothesize that HCPs’ preference for the online modality has probably increased since the occurrence of the Covid-19 pandemic. Online resources have the advantage of being available “just in time,” exactly when HCPs need it and are ready to integrate this in their practice and skill set. This immediacy feature is coherent with an important adult learning theory principle that suggests that learners are interested in acquiring knowledge that has immediate relevance and effect.
      • Knowles M.S.
      • Holton III, E.F.
      • Swanson R.A.
      • Robinson P.A.
      The Adult Learner: The Definitive Classic in Adult Education and Human Resource Development.

      Strengths and Limitations

      To our knowledge, the sample size of this study is the largest and includes the most diversified population of HCPs to date to characterize their level of familiarity and perspectives on the concept of PRS and the risk-stratified BC screening approach. The recruitment method was multifaceted and was primarily through professional associations and health care institutions. Such a recruitment scale is particularly impressive in the context of the Covid-19 pandemic.
      Nevertheless, it is important to recognize the limitations of our study. Although our questionnaire was designed to be of 15-minute duration to accommodate a target population with many competing priorities, a more detailed knowledge status, professional practice situation, and learning need collection tool would be required because this is a crucial step in establishing sound CPD curriculum.
      • Grant J.
      Learning needs assessment: assessing the need.
      It is important to recognize that an online recruitment and data collection strategy may result in a greater proportion of participants preferring electronic CPD. Our sample distribution is not representative of the Canadian HCP population. Supplemental Tables 1–3 contrasts some of the demographics of participants with that of the Canadian physicians and nurses workforce. Our sample had a higher proportion of female and of professionals from the province of Québec than the National statistics.

      Canadian Institute for Health Information. Health workforce. Canadian Institute for Health Information. Published 2021. Accessed June 9, 2022. https://www.cihi.ca/en/health-workforce

      However, the proportion of participating physicians who indicated family medicine as their medical specialty is comparable to the National statistics.
      We believe though that our results offer an indication that professionals not trained in genetics are largely unfamiliar with the concept of PRS, believe their knowledge to be inadequate regarding risk-stratified BC screening, and that proper CPD should be planned. In some provinces, our recruitment was more frequently done through a snowball approach within the vast network of our collaborators. This might have resulted in the recruitment of people already interested in and knowledgeable of the concept of PRS and risk-stratified BC screening approach. If this selection bias is present, it would mean that the real level of familiarity with the concept of PRS and knowledge of risk-stratified BC screening of HCPs is even lower than what we observed.

      Conclusion

      Current use of PRS testing is at an early stage of integration.
      Polygenic Risk Score Task Force of the International Common Disease Alliance
      Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps.
      Although the risk-stratified BC screening based on the information such as the PRS is not yet part of any Canadian provinces or territories’ public health measures, it is currently undergoing effectiveness implementation studies in Canada,
      • Brooks J.D.
      • Nabi H.H.
      • Andrulis I.L.
      • et al.
      Personalized risk assessment for prevention and early detection of breast cancer: integration and implementation (PERSPECTIVE I&I).
      as well as in the United States
      • Esserman L.J.
      • Investigators Athena
      WISDOM Study
      The WISDOM Study: breaking the deadlock in the breast cancer screening debate.
      and Europe.
      Horizon 2020
      MyPeBS Personalising Breast Screening. MyPeBS.
      There is therefore a window of opportunity for professional associations, health care institutions, and public health or government agencies overseeing screening programs to proactively plan for knowledge dissemination strategies that will effectively support HCPs involved at different contact points in the integration of this emerging genomics strategy.
      • Esquivel-Sada D.
      • Lévesque E.
      • Hagan J.
      • Knoppers B.M.
      • Simard J.
      Envisioning implementation of a personalized approach in breast cancer screening programs: stakeholder perspectives.
      ,
      • Yanes T.
      • McInerney-Leo A.M.
      • Law M.H.
      • Cummings S.
      The emerging field of polygenic risk scores and perspective for use in clinical care.
      The fact that a lack of knowledge has been identified as the most frequent barrier to the implementation of genetics and genomics in practices
      • Morrow A.
      • Chan P.
      • Tucker K.M.
      • Taylor N.
      The design, implementation, and effectiveness of intervention strategies aimed at improving genetic referral practices: a systematic review of the literature.
      justifies the relevance of investing in workforce preparation and CPD activities tailored to HCPs’ existing knowledge and clinical practice needs.

      Data Availability

      Additional data are available from the corresponding author upon request.

      Acknowledgments

      The PERSPECTIVE I&I project is funded by the Government of Canada, Canada through GenomeCanada (#13529) and the Canadian Institutes of Health Research, Canada (#155865), the Ministère de l’Économie et de l'Innovation du Québec through Genome Québec, the Quebec Breast Cancer Foundation, Canada , the CHU de Québec Foundation, and the Ontario Research Fund. 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.

      Author Information

      Conceptualization: J.L., A.-C.B., C.M.-B., M.D., N.P., J.D.B., M.J.W., J.C., L.E., K.B., A.T., L.L.-C., L.L., G.D., Y.J., B.M.K., A.M.C., J.S., H.N.; Data Curation: J.L., A.-C.B., C.M.-B.; Formal Analysis: J.L., A.-C.B., C.M.-B., H.N.; Funding Acquisition: J.S., A.M.C.; Methodology: J.L., A.-C.B., C.M.-B., M.D., N.P., J.D.B., M.J.W., J.C., L.E., K.B., A.T., L.L.-C., L.L., G.D., Y.J., B.M.K., A.M.C., J.S., H.N.; Project Administration: J.L., H.N.; Resources: H.N., J.S., A.M.C.; Supervision: H.N.; Writing-original draft: J.L., A.-C.B., C.M.-B., H.N.; Writing-review and editing: J.L., A.-C.B., C.M.-B., M.D., N.P., J.D.B., M.J.W., J.C., L.E., K.B., A.T., L.L.-C., L.L., G.D., Y.J., B.M.K., A.M.C., J.S., H.N.

      Ethics Declaration

      The study was approved by the Institutional Review Board of CHU de Québec-Université Laval (2021-5136). Informed consent was obtained from all participants when they opened the survey link. Data were collected in a completely anonymous fashion—the information never had identifiers associated with it.

      Conflict of Interest

      The authors declare no conflict of interest.

      Supplementary Material

      References

        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • et al.
        Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
        CA A Cancer J Clin. 2021; 71: 209-249https://doi.org/10.3322/caac.21660
        • Dibden A.
        • Offman J.
        • Duffy S.W.
        • Gabe R.
        Worldwide review and meta-analysis of cohort studies measuring the effect of mammography screening programmes on incidence-based breast cancer mortality.
        Cancers. 2020; 12: 976https://doi.org/10.3390/cancers12040976
        • Lauby-Secretan B.
        • Scoccianti C.
        • Loomis D.
        • et al.
        Breast-cancer screening—viewpoint of the IARC Working Group.
        N Engl J Med. 2015; 372: 2353-2358https://doi.org/10.1056/NEJMsr1504363
        • van den Broek J.J.
        • Schechter C.B.
        • van Ravesteyn N.T.
        • et al.
        Personalizing breast cancer screening based on polygenic risk and family history.
        J Natl Cancer Inst. 2021; 113: 434-442https://doi.org/10.1093/jnci/djaa127
        • Brooks J.D.
        • Nabi H.H.
        • Andrulis I.L.
        • et al.
        Personalized risk assessment for prevention and early detection of breast cancer: integration and implementation (PERSPECTIVE I&I).
        J Pers Med. 2021; 11: 511https://doi.org/10.3390/jpm11060511
        • Esserman L.J.
        • Investigators Athena
        • WISDOM Study
        The WISDOM Study: breaking the deadlock in the breast cancer screening debate.
        NPJ Breast Cancer. 2017; 3: 34https://doi.org/10.1038/s41523-017-0035-5
        • Horizon 2020
        MyPeBS Personalising Breast Screening. MyPeBS.
        (Accessed September 29, 2021.)
        • Zhang X.
        • Rice M.
        • Tworoger S.S.
        • et al.
        Addition of a polygenic risk score, mammographic density, and endogenous hormones to existing breast cancer risk prediction models: A nested case-control study.
        PLoS Med. 2018; 15e1002644https://doi.org/10.1371/journal.pmed.1002644
        • Mavaddat N.
        • Michailidou K.
        • Dennis J.
        • et al.
        Polygenic risk scores for prediction of breast cancer and breast cancer subtypes.
        Am J Hum Genet. 2019; 104: 21-34https://doi.org/10.1016/j.ajhg.2018.11.002
        • Chowdhury S.
        • Henneman L.
        • Dent T.
        • et al.
        Do health professionals need additional competencies for stratified cancer prevention based on genetic risk profiling?.
        J Pers Med. 2015; 5: 191-212https://doi.org/10.3390/jpm5020191
        • Kirk M.
        • Calzone K.
        • Arimori N.
        • Tonkin E.
        Genetics-genomics competencies and nursing regulation.
        J Nurs Scholarsh. 2011; 43: 107-116https://doi.org/10.1111/j.1547-5069.2011.01388.x
        • Polygenic Risk Score Task Force of the International Common Disease Alliance
        Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps.
        Nat Med. 2021; 27: 1876-1884https://doi.org/10.1038/s41591-021-01549-6
        • McGuinness M.
        • Fassi E.
        • Wang C.
        • Hacking C.
        • Ellis V.
        Breast cancer polygenic risk scores in the clinical cancer genetic counseling setting: current practices and impact on patient management.
        J Genet Couns. 2021; 30: 588-597https://doi.org/10.1002/jgc4.1347
        • Smit A.K.
        • Sharman A.R.
        • Espinoza D.
        • et al.
        Knowledge, views and expectations for cancer polygenic risk testing in clinical practice: a cross-sectional survey of health professionals.
        Clin Genet. 2021; 100: 430-439https://doi.org/10.1111/cge.14025
        • Esquivel-Sada D.
        • Lévesque E.
        • Hagan J.
        • Knoppers B.M.
        • Simard J.
        Envisioning implementation of a personalized approach in breast cancer screening programs: stakeholder perspectives.
        Healthc Policy. 2019; 15: 39-54https://doi.org/10.12927/hcpol.2019.26072
        • Puzhko S.
        • Gagnon J.
        • Simard J.
        • Knoppers B.M.
        • Siedlikowski S.
        • Bartlett G.
        Health professionals’ perspectives on breast cancer risk stratification: understanding evaluation of risk versus screening for disease.
        Public Health Rev. 2019; 40: 2https://doi.org/10.1186/s40985-019-0111-5
        • Bégin M.
        Medicare: Canada’s right to health.
        Optimum Pub International, 1988
        • Canadian Institute for Health Information
        Exploring the 70/30 Split: How Canadaís Health Care System Is Financed.
        Canadian Institute for Health Information, 2005
        • Government of Canada
        Health care in Canada: Access our universal health care system. Government of Canada. Accessed June 8, 2022.
      1. Public Health Agency of Canada. Organized breast cancer screening programs in Canada. Report on program performance in 2005 and 2006. Published 2011. Accessed June 8, 2022. https://www.canada.ca/content/dam/phac-aspc/migration/phac-aspc/cd-mc/publications/cancer/obcsp-podcs05/pdf/breast-cancer-report-eng.pdf

        • Blood K.A.
        • McCullum M.
        • Wilson C.
        • Cheifetz R.E.
        Hereditary breast cancer in British Columbia: outcomes from BC Cancer’s High-Risk Clinic.
        BCMJ. 2018; 60: 40-46
      2. Cancer care Ontario (CCO). Accessed June 9, 2022.
      3. Canadian Task Force on Preventive Health Care. Breast cancer—clinician mammography recommendation. Published 2019. Accessed June 8, 2022. https://canadiantaskforce.ca/breast-cancer-clinician-mammography-recommendation/

      4. Government of Canada. Canada’s health care system. Government of Canada. Published 2019. Accessed July 20, 2022. https://www.canada.ca/en/health-canada/services/health-care-system/reports-publications/health-care-system/canada.html#a11

      5. Gagnon J, Lévesque E, Clinical Advisory Committee on Breast Cancer Screening and Prevention, et al. Recommendations on breast cancer screening and prevention in the context of implementing risk stratification: impending changes to current policies. Curr Oncol. 2016;23(6):e615–e625. http://doi.org/10.1093/jnci/djw290

        • Shieh Y.
        • Eklund M.
        • Madlensky L.
        • et al.
        Breast cancer screening in the precision medicine era: risk-based screening in a population-based trial.
        J Natl Cancer Inst. 2017; 109https://doi.org/10.1093/jnci/djw290
        • Koitsalu M.
        • Sprangers M.A.
        • Eklund M.
        • et al.
        Public interest in and acceptability of the prospect of risk-stratified screening for breast and prostate cancer.
        Acta Oncol. 2016; 55: 45-51https://doi.org/10.3109/0284186X.2015.1043024
        • Harris P.A.
        • Taylor R.
        • Thielke R.
        • Payne J.
        • Gonzalez N.
        • Conde J.G.
        Research Electronic Data Capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support.
        J Biomed Inform. 2009; 42: 377-381https://doi.org/10.1016/j.jbi.2008.08.010
        • Enders C.K.
        Applied Missing Data Analysis.
        Guilford Press, 2010
        • Marcon A.R.
        • Bieber M.
        • Caulfield T.
        Representing a “revolution”: how the popular press has portrayed personalized medicine.
        Genet Med. 2018; 20: 950-956https://doi.org/10.1038/gim.2017.217
        • Knoppers B.M.
        • Bernier A.
        • Granados Moreno P.
        • Pashayan N.
        Of screening, stratification, and scores.
        J Pers Med. 2021; 11: 736https://doi.org/10.3390/jpm11080736
        • McCauley M.P.
        • Marcus R.K.
        • Strong K.A.
        • Visotcky A.M.
        • Shimoyama M.E.
        • Derse A.R.
        Genetics and genomics in clinical practice: the views of Wisconsin physicians.
        WMJ. 2017; 116: 69-74
        • Marzuillo C.
        • De Vito C.
        • D’Addario M.
        • et al.
        Are public health professionals prepared for public health genomics? A cross-sectional survey in Italy.
        BMC Health Serv Res. 2014; 14: 239https://doi.org/10.1186/1472-6963-14-239
        • Paul J.L.
        • Leslie H.
        • Trainer A.H.
        • Gaff C.
        A theory-informed systematic review of clinicians’ genetic testing practices.
        Eur J Hum Genet. 2018; 26: 1401-1416https://doi.org/10.1038/s41431-018-0190-7
        • Owusu Obeng A.
        • Fei K.
        • Levy K.D.
        • et al.
        Physician-reported benefits and barriers to clinical implementation of genomic medicine: a multi-site IGNITE-network survey.
        J Pers Med. 2018; 8: 24https://doi.org/10.3390/jpm8030024
        • Mavaddat N.
        • Pharoah P.D.
        • Michailidou K.
        • et al.
        Prediction of breast cancer risk based on profiling with common genetic variants.
        J Natl Cancer Inst. 2015; 107: djv036https://doi.org/10.1093/jnci/djv036
        • Pashayan N.
        • Duffy S.W.
        • Neal D.E.
        • et al.
        Implications of polygenic risk-stratified screening for prostate cancer on overdiagnosis.
        Genet Med. 2015; 17: 789-795https://doi.org/10.1038/gim.2014.192
        • Rahma A.T.
        • Elsheik M.
        • Ali B.R.
        • et al.
        Knowledge, attitudes, and perceived barriers toward genetic testing and pharmacogenomics among healthcare workers in the United Arab Emirates: a cross-sectional study.
        J Pers Med. 2020; 10: 216https://doi.org/10.3390/jpm10040216
        • Lopes-Júnior L.C.
        • Carvalho Júnior P.M.
        • de Faria Ferraz V.E.
        • Nascimento L.C.
        • Van Riper M.
        • Flória-Santos M.
        Genetic education, knowledge and experiences between nurses and physicians in primary care in Brazil: a cross-sectional study.
        Nurs Health Sci. 2017; 19: 66-74https://doi.org/10.1111/nhs.12304
        • Ha V.T.D.
        • Frizzo-Barker J.
        • Chow-White P.
        Adopting clinical genomics: a systematic review of genomic literacy among physicians in cancer care.
        BMC Med Genomics. 2018; 11: 18https://doi.org/10.1186/s12920-018-0337-y
        • Hann K.E.J.
        • Fraser L.
        • Side L.
        • et al.
        Health care professionals’ attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.
        BMC Womens Health. 2017; 17: 132https://doi.org/10.1186/s12905-017-0488-6
        • Chow-White P.
        • Ha D.
        • Laskin J.
        Knowledge, attitudes, and values among physicians working with clinical genomics: a survey of medical oncologists.
        Hum Resour Health. 2017; 15: 42https://doi.org/10.1186/s12960-017-0218-z
        • Harding B.
        • Webber C.
        • Ruhland L.
        • et al.
        Primary care providers’ lived experiences of genetics in practice.
        J Community Genet. 2019; 10: 85-93https://doi.org/10.1007/s12687-018-0364-6
        • Carroll J.C.
        • Allanson J.
        • Morrison S.
        • et al.
        Informing integration of genomic medicine into primary care: an assessment of current practice, attitudes, and desired resources.
        Front Genet. 2019; 10: 1189https://doi.org/10.3389/fgene.2019.01189
        • Nisselle A.
        • King E.A.
        • McClaren B.
        • et al.
        Measuring physician practice, preparedness and preferences for genomic medicine: a national survey.
        BMJ Open. 2021; 11e044408https://doi.org/10.1136/bmjopen-2020-044408
        • Knowles M.S.
        • Holton III, E.F.
        • Swanson R.A.
        • Robinson P.A.
        The Adult Learner: The Definitive Classic in Adult Education and Human Resource Development.
        9th ed. Taylor & Francis Group, 2020
        • Grant J.
        Learning needs assessment: assessing the need.
        BMJ. 2002; 324: 156-159https://doi.org/10.1136/bmj.324.7330.156
      6. Canadian Institute for Health Information. Health workforce. Canadian Institute for Health Information. Published 2021. Accessed June 9, 2022. https://www.cihi.ca/en/health-workforce

        • Yanes T.
        • McInerney-Leo A.M.
        • Law M.H.
        • Cummings S.
        The emerging field of polygenic risk scores and perspective for use in clinical care.
        Hum Mol Genet. 2020; 29: R165-R176https://doi.org/10.1093/hmg/ddaa136
        • Morrow A.
        • Chan P.
        • Tucker K.M.
        • Taylor N.
        The design, implementation, and effectiveness of intervention strategies aimed at improving genetic referral practices: a systematic review of the literature.
        Genet Med. 2021; 23: 2239-2249https://doi.org/10.1038/s41436-021-01272-0