Implementation of Risk-Stratified Breast Cancer Prevention With a Polygenic Risk Score Test in Clinical Practice.
Background: Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have iden...
| Published in: | Breast Cancer: Basic & Clinical Research pp. 1 - 14 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | equations & formulas research tables/charts Journal Article |
| Published: |
Sage Publications Inc.
10/12/2023
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=172987485&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 172987485 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11782234 B078 jtl: Breast Cancer: Basic & Clinical Research issn: 11782234 maglogo: Y pubinfo: dt: 10/12/2023 pid: 344 pub: Sage Publications Inc. place: Thousand Oaks, California artinfo: ui: 172987485 172987485 172987485 10.1177/11782234231205700 172987485 ppf: 1 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Implementation of Risk-Stratified Breast Cancer Prevention With a Polygenic Risk Score Test in Clinical Practice. aug: au: Padrik, Peeter Puustusmaa, Mikk Tõnisson, Neeme Kolk, Berit Saar, Regina Padrik, Anna Tasa, Tõnis affil: OÜ Antegenes, Tartu, Estonia sug: subj: Breast Neoplasms Diagnosis Breast Neoplasms Prevention and Control Cancer Screening Methods Risk Assessment Polymorphism, Single Nucleotide Medical Practice Program Implementation Human Female Retrospective Design Prediction Models Cox Proportional Hazards Model Regression Descriptive Statistics Female ab: Background: Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have identified numerous genetic variants (single-nucleotide polymorphisms [SNPs]) associated with BC. The effects of SNPs are combined into a polygenic risk score (PRS) as a risk prediction tool. Objectives: We aimed to develop a clinical-grade PRS test suitable for BC risk-stratified screening with clinical recommendations and implementation in clinical practice. Design and methods: In the first phase of our study, we gathered previously published PRS models for predicting BC risk from the literature and validated them using the Estonian Biobank and UK Biobank data sets. We selected the best performing model based on prevalent data and independently validated it in both incident data sets. We then conducted absolute risk simulations, developed risk-based recommendations, and implemented the PRS test in clinical practice. In the second phase, we carried out a retrospective analysis of the PRS test's performance results in clinical practice. Results: The best performing PRS included 2803 SNPs. The C-index of the Cox regression model associating BC status with PRS was 0.656 (SE = 0.05) with a hazard ratio of 1.66. The PRS can stratify individuals with more than a 3-fold risk increase. A total of 2637 BC PRS tests have been performed for women between the ages 30 and 83. Results in clinical use overlap well with expected PRS performance with 5.7% of women with more than 2-fold and 1.4% with more than 3-fold higher risk than the population average. Conclusion: The PRS test separates different BC risk levels and is feasible to implement in clinical practice. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|