Using Genetic Risk Scores in Cancer Screening: Are We There Yet?

July 5, 2018 by Megan C Roberts, Division of Cancer Control and Population Sciences, The National Cancer Institute, and Muin J. Khoury, Office of Public Health Genomics, Centers for Disease Control and Prevention
a person looking at data and chromosomes and a cancer cell

a person looking at data and chromosomes and a cancer cell

Precision screening seeks to measure benefits and risks of screening more accurately by accounting for individual-level differences, such as those in genetics, environment, and lifestyle factors. Accounting for individual differences may allow risk stratification to identify persons whose cancer risk is high enough that the benefits of screening would outweigh potential harms or whose cancer risk is low enough not to recommend screening. Within the context of breast cancer screening, stratifying by risk could be important in providing high quality prevention and care. Evidence demonstrates that while breast cancer screening reduces mortality, it also exposes women to potential harms related to overdiagnosis, particularly among women who are at low risk of breast cancer.

Accounting for genetic differences may allow risk stratification to identify persons whose cancer risk is high enough that the benefits of screening would outweigh potential harms…

Risk stratification for cancer screening is common. Most guidelines target screening by various individual-level factors, such as age and gender. In the era of precision medicine, genetic risk scores, based on the combined additive effects of many genetic variants, are an emerging example of a potential risk stratification tool for population screening. A paper by Pashayan and colleagues and an editorial in the most recent edition of JAMA Oncology illustrate some of the promises and challenges for implementing genetic risk scores in cancer screening. Pashayan and colleagues examined the cost-effectiveness of using polygenic risk scores to stratify women for breast cancer screening in the United Kingdom and found that risk-targeted screening is less costly than age-based screening and with fewer overdiagnoses. The authors found that risk-targeted screening at the 70thpercentile risk cut-off would cost £537,985 less than age-based screening, with 71% fewer overdiagnoses. When screening was targeted at women with a risk threshold of 70% or less, the number of cancer deaths avoided through screening was less than the number of overdiagnoses. This study suggests that a genetic risk score-stratified screening program in which those with low risk are not offered breast cancer screening would be a viable alternative to age-based screening.

While these findings provide evidence for using genetic risk scores in precision screening in breast cancer, several factors need to be considered before implementing such an approach.

Level of evidence necessary to implement precision screening. Some experts believe that randomized controlled trials would be needed, while others believe that observational studies and statistical modelling would be sufficient.
Limited evidence regarding the acceptability and feasibility of using polygenic risk scores on a population level to determine breast cancer screening eligibility. Issues of acceptability will be context dependent and may or may not apply in other countries including the United States, which has unique ethical, legal and social implications for genetic testing within the context of population-based cancer screening.
Other barriers, such as costs, low provider and patient knowledge, and low organizational readiness for the collection of genetic information. These barriers could be worse in underserved populations who have lower access to genomic technologies and are underrepresented in genomic research.
Challenges from de-implementing breast cancer screening among women with low polygenic risk scores. Research to determine the best strategies of implementing (de-implementing) screening strategies within the low genetic risk group will be crucial for effective implementation of precision screening. Moving forward, addressing these challenges and others will be necessary to improve population health through precision screening.