Since the advent of screening mammograms in the late 20th century, breast cancer screening recommendations have remained largely unchanged and rely on age as the main criterion to guide screening. While there are new breast cancer risk prediction tools, little is known about how clinicians should use breast cancer risk to guide patients in decision-making for screening and prevention.
The Women Informed to Screen Depending On Measures of risk (WISDOM) Study began in 2016, aiming to provide evidence on risk-based screening. This randomized trial compares the efficacy, safety, acceptability, and health care value of personalized breast cancer screening versus annual mammography. Participants receiving personalized screening undergo assessments and testing to construct a polygenic risk score (PRS). This score predicts breast cancer risk based on the combined effects of common genetic variants.
A study in Genome Medicine from Dr. Yiwey Shieh, assistant professor of population health sciences and medicine, and colleagues outlined the first wave of results from the nationwide implementation of breast cancer PRS for personalized screening. Researchers evaluated data from 21,631 participants aged 40 to 74.
Results showed that a higher PRS was associated with a greater extent of family history and higher breast density. Incorporating PRS into a clinical risk model changed the trial’s screening recommendations for 14 percent of women aged 40 to 49 and for 10 percent of women aged 50 to 74. Altogether, similar PRS distributions were observed across demographic subgroups and consistent with the expected associations with breast density and family history, suggesting that the PRS accurately captured genetic predisposition for breast cancer.
“Our findings are important to the field of translational genomics, as they highlight a path toward clinical adoption of PRS, as well as to the field of preventive oncology,” said Dr. Shieh. “The use of PRS can potentially inform the delivery of cancer screening and prevention based on individual risk rather than on age alone.”
Ongoing iterations of the WISDOM Study will allow researchers to identify additional methods for PRS construction.
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