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Assessment of polygenetic risk score for breast cancer

Polygenetic risk score assessment for breast cancer

Polygenetic risk score

Tone Hovda, Phd

The study aims to evaluate the impact of implementing population-based genetics testing strategy for breast cancer precision prevention using the polygenic risk score and monogenic pathogenic variant (MPV) testing in the Norwegian healthcare setting.

The study will recruit women age 40-50 referred for clinical mammography at the Vestre Viken Breast Center, with mammographic density BI-RADS a or d. After informed consent, saliva from the participants will be sampled and tested for polygenetic risk score (PRS) for breast cancer. The participants will be recommended future mammographic screening based on the PRS (standard screening, or more frequent/start at earlier age). The participants family history of cancer will be assessed, and if indicated, the participants will be referred for full genetic counselling/testing. The study will follow the women for 10 years for development of breast cancer as well as compliance to the recommended follow-up.

Clinical Pilot Study for Personalized Risk-based Breast Cancer Screening

Polygenetic breast cancer risk score (PRS) as a numeric value with 10 percentile, as absolute 10-year breast cancer risk, and as relative risk compared with average women at the same age

Percentage and frequencies of participants following their individual screening recommendations

Distribution of PRS among participants with increased breast cancer risk based on family history

Questionnaries on experience with the sampling process and feedback on a categorical scale (totally disagree, disagree, neutral, agree, totally agree)

Oslo University Hospital

Vestre Viken Hospital Trust

Breast cancer risk measurement, screening recommendations and shared decision making

Risk based screening

The overall objective is to assess the acceptability and feasibility of offering personalized breast cancer (BC) screening.

The specific objectives are: 1) To design an information system; 2) To evaluate the barriers and facilitators of the coordination of health care services and the screening program; 3) To develop a proof of concept of personalized screening; and 4) To evaluate cost-effectiveness.

Methodology:

1. Prototype information system with basal and longitudinal variables relevant to a personalized screening system;
2. Qualitative study with focus groups and survey. The attitude and acceptability on a sample of 210 health professionals will be assessed;
3. Prospective observational study, for proof of concept. Participants will be professionals working in Primary Care, Population Breast Screening Program, or Hospital Breast Unit. It will include 385 women, aged 40-50 from the city of Lleida. Various indicators of acceptability and feasibility will be assessed in women and health professionals;
4. Probabilistic analytical models will be used to evaluate cost-effectiveness.

The present protocol addresses the specific objective number 3, the proof of concept of personalised screening.

Expected results: The investigators expect to provide valuable and necessary information for the design of personalized screening.

Assessment of Feasibility and Acceptability of Personalized Breast Cancer Screening

Personalized Breast Cancer Screening: Assessment of Its Feasibility and Acceptability in the National Health System

Attitude scale with three items, one about the frequency of screening exams (ranges from 1 to 5). The other two items ask if participants are satisfied of being invited more/less frequently, in case that they have a higher/lower risk of breast cancer than the average women. They also range from 1 to 5. Total scores can range from 3 to 15. Higher scores indicate more positive attitudes. A positive attitude is defined as a total score greater or equal to 12. Adapted from Hersch et al. (2015)

Categorical variable with five categories: definitely will, likely to, unsure, not likely to, definitely will not. The absolute and relative frequencies of the five categories will be obtained. In addition, the variable will be dichotomized as intending to participate (definitely or likely) or not. Adapted from Hersch et al. (2015)

Satisfaction Likert scale with one item that ranges from 1 to 5: not at all satisfied (1), extremely satisfied (5). Following the Sekhon et al. review (2017)

General attitudes scale towards screening mammography. It will be measured using five items adapted from Hersch et al. (2015). Each item ranges from 1 to 5. Total scores can range from 5 to 25. A positive attitude is defined as a total score greater or equal to 20. Higher scores indicate more positive attitudes. Adapted from Hersch et al. (2015)

One categorical variable with four categories. It asks if the measure of breast cancer risk will do more harm than good, more good than harm, it depends, do not know. The absolute and relative frequencies of the four categories will be obtained. Following the Sekhon et al. review (2017)

Three categorical variables with five categories, ranging from strongly disagree (1) to strongly agree (5). First variable: The information about the individual risk of breast cancer provides calmness. Second variable: Receiving information about risks produces anxiety. Third variable: The information about the individual risk of breast cancer makes me worry. The scores of the three items will not be added as a scale, they will be reported separately. Adapted from Hersch et al. (2015)

Categorical variable with three categories. It asks what type of screening the participants would choose (personalized risk-based or "one-size-fits-all")

Eleven conceptual knowledge questions (Yes/No) and four numerical knowledge questions with categories on the effect of screening. A total of 22 marks could be obtained, 11 coming from the questions on conceptual knowledge and 11 coming from the questions on numerical knowledge that measured absolute and relative values of the screening outcomes. The threshold to define adequate knowledge is to score at least 50% of the available marks, including at least one numerical mark, on all the three screening outcome subscales that refer to mortality reduction, overdiagnosis, and false positives. Adapted from Hersch et al. (2015)

O'Connor Decisional Conflict Scale, 10-item low literacy version, on a scale from 0 (no decisional conflict) to 100 (extreme decisional conflict). Scores less than 25 are associated with implementing decisions; score exceeding 37.5 are associated with decision delay or feeling unsure about implementation.

Three Likert scale statements rated from 1 (not at all confident) to 5 (very confident). A total score is obtained summing the scores of the three items and dividing by three.

Adapted from the O'Connor Decision Self-Efficacy Scale

Six-item short form of the Spielberger State Trait Anxiety Inventory (STAI) on a scale from 20 to 80, with higher scores indicating greater levels of anxiety. To calculate the total STAI score, reverse scoring of the positive items (calm, relaxed, content), sum all six scores and multiply total score by 20/6.

Women will be asked how important it is for them to consider the chances of (1) avoiding breast cancer death, (2) being diagnosed and treated for a cancer that is not harmful, and (3) having a false positive. The four response options range from very important (1) to not at all important (4). The scores of the three items will not be added as a scale, they will be reported separately. According to Hersch et al. (2015)

Four items ranging from strongly disagree (1) to strongly agree (5). Total scores can range from 4 to 20. Higher scores indicate higher self-efficacy. Following the Sekhon et al. review (2017)

It will be measured using five items. Each item ranges from 1 to 5. Total scores can range from 5 to 25. A positive assessment is defined as a total score greater or equal to 20. Higher scores indicate more positive experience assessment. Following the Sekhon et al. review (2017)

Confidence Likert scale with one item ranging from very low confidence (1) to very high confidence (5) . Following the Sekhon et al. review (2017)

Two categorical variables with five categories each, ranging from strongly disagree (1) to strongly agree (5). First variable: I understood the information I received about my risk of breast cancer in relation to women of my age. Second variable: I have understood the recommendations given to me about the screening of breast cancer in the coming years, based on my risk of breast cancer. The scores of the two items will not be added as a scale, they will be reported separately. Following the Sekhon et al. review (2017)

Continuous variable, number of minutes. Recorded by the participant doctors

Number of women that accept to participate divided by number of women contacted

Number of women that complete the different phases divided by number of participating women

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Clinical Pilot Study for Personalized Risk-based Breast Cancer Screening	NCT05731453	Breast Cancer	Polygenetic ris...	40 Years - 50 Years	Vestre Viken Hospital Trust
Assessment of Feasibility and Acceptability of Personalized Breast Cancer Screening	NCT03791008	Breast Cancer	Risk based scre...	40 Years - 50 Years	Institut de Recerca Biomèdica de Lleida

Spots Global Cancer Trial Database for risk based screening