J Clin Oncol. 2024 Feb 29. IF: 45.3
Comprehensive Inherited Risk Estimation for Risk-Based Breast Cancer Screening in Women. OPEN ACCESS
Mars N, Kerminen S, Tamlander M, Pirinen M, Jakkula E, Aaltonen K, Meretoja T, Heinavaara S, Widén E, Ripatti S; FinnGen.
University of Helsinki, Helsinki, Finland; Broad Institute of MIT and Harvard, Cambridge, MA; Helsinki University Hospital, Helsinki, Finland; Finnish Cancer Registry, Cancer Society of Finland, Helsinki, Finland.
PURPOSE: Family history (FH) and pathogenic variants (PVs) are used for guiding risk surveillance in selected high-risk women but little is known about their impact for breast cancer screening on population level. In addition, polygenic risk scores (PRSs) have been shown to efficiently stratify breast cancer risk through combining information about common genetic factors into one measure.
METHODS: In longitudinal real-life data, we evaluate PRS, FH, and PVs for stratified screening. Using FinnGen (N = 117,252), linked to the Mass Screening Registry for breast cancer (1992-2019; nationwide organized biennial screening for age 50-69 years), we assessed the screening performance of a breast cancer PRS and compared its performance with FH of breast cancer and PVs in moderate- (CHEK2)- to high-risk (PALB2) susceptibility genes.
RESULTS: Effect sizes for FH, PVs, and high PRS (>90th percentile) were comparable in screening-aged women, with similar implications for shifting age at screening onset. A high PRS identified women more likely to be diagnosed with breast cancer after a positive screening finding (positive predictive value [PPV], 39.5% [95% CI, 37.6 to 41.5]). Combinations of risk factors increased the PPVs up to 45% to 50%. A high PRS conferred an elevated risk of interval breast cancer (hazard ratio [HR], 2.78 [95% CI, 2.00 to 3.86] at age 50 years; HR, 2.48 [95% CI, 1.67 to 3.70] at age 60 years), and women with a low PRS (<10th percentile) had a low risk for both interval- and screen-detected breast cancers.
CONCLUSION: Using real-life screening data, this study demonstrates the effectiveness of a breast cancer PRS for risk stratification, alone and combined with FH and PVs. Further research is required to evaluate their impact in a prospective risk-stratified screening program, including cost-effectiveness.
KEY OBJECTIVE: The current approach to population breast cancer screening uses a one-size-fits-all regimen, yet studies on inherited risk factors, including polygenic risk scores (PRS) for breast cancer, family history, and pathogenic variants (PVs) in susceptibility genes, suggest the potential for personalized screening on the basis of individual risk profiles. How do such inherited risk factors, particularly the PRS, which is a more recently identified risk factor, perform in real-life screening data?
KNOWLEDGE GENERATED: The breast cancer PRS served for risk stratification of breast cancer screening both alone and combined with FH and PVs. A high PRS correlated with a high positive predictive value for breast cancer screening and conferred an elevated risk for interval breast cancer.
RELEVANCE: Future trials attempting to personalize type and schedule of breast cancer screening should strongly consider incorporation of a PRS along with other risk factors.
PMID: 38422475
DOI: 10.1200/JCO.23.00295
NOTE: This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
J Clin Oncol. 2024 Feb 29. IF: 45.3
Toward Application of Polygenic Risk Scores to Both Enhance and Deintensify Breast Cancer Screening.
Maxwell KN, Domchek SM.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA; Corporal Michael Crescenz Veterans Affairs Medical Center, Philadelphia, PA.
PMID: 38422469
DOI: 10.1200/JCO.24.00029
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