核心概念
Combining polygenic risk scores with family history and pathogenic variants improves breast cancer risk stratification, enabling more personalized screening approaches.
摘要
The content discusses the potential of using polygenic risk scores (PRS) alongside family histories and pathogenic gene variants to enhance breast cancer risk assessment and screening strategies.
Key highlights:
- Researchers in Finland used a nationwide genetic database to calculate PRS for 117,252 women and linked the scores to their breast cancer outcomes.
- A high PRS (top 10%) was associated with over a 2-fold higher risk of breast cancer compared to a lower PRS (below 90%), similar to the risk conferred by pathogenic variants and positive family histories.
- Combining a high PRS with positive family history or pathogenic variants increased the positive predictive value for a breast cancer diagnosis after a positive screening mammogram to 44.6% and 50.6%, respectively.
- High PRS was also linked to a 2-fold higher risk of interval breast cancers and higher risk of bilateral breast cancers during screening ages, suggesting the need for shorter screening intervals or earlier screening for these individuals.
- Women with low PRS (bottom 10%) had very low risk of interval and screen-detected cancers, potentially allowing for less frequent screening.
- The study demonstrates the value of incorporating PRS into breast cancer risk stratification, optimizing screening strategies by combining genetic, family history, and other risk factors.
統計資料
A high polygenic risk score (top 10%) was associated with over a 2-fold higher risk of any breast cancer before, during, and after screening age (HR 2.50, 2.38, and 2.11, respectively).
Pathogenic variants led to a 3.13, 2.30, and 1.95-fold higher risk at the same timepoints.
Positive family history led to a 1.97, 1.96, and 1.68-fold higher risk at the same timepoints.
A high polygenic risk score had a 39.5% positive predictive value for a breast cancer diagnosis after a positive screening mammogram.
Combining a high polygenic risk score with positive family history increased the positive predictive value to 44.6%.
Combining a high polygenic risk score with pathogenic variants increased the positive predictive value to 50.6%.
A high polygenic risk score was associated with a 4.71-fold higher risk of bilateral breast cancer during screening ages.
引述
"Compared with a lower polygenic risk score (below 90%), a high polygenic risk score — a score in the top 10% — was associated with more than a twofold higher risk for any breast cancer before, during, and after screening age."
"A high polygenic risk score had a positive predictive value of 39.5% for a breast cancer diagnosis after a positive screening mammography, about the same as positive family history (35.5%) and pathogenic variants (35.9%)."
"Combining a high polygenic risk score with a positive family history increased the positive predictive value to 44.6% and with pathogenic variant carriers increased the positive predictive value to 50.6%."