The WISDOM Study: breaking the deadlock in the breast cancer screening debate

Abstract

There are few medical issues that have generated as much controversy as screening for breast cancer. In science, controversy often stimulates innovation; however, the intensely divisive debate over mammographic screening has had the opposite effect and has stifled progress. The same two questions—whether it is better to screen annually or bi-annually, and whether women are best served by beginning screening at 40 or some later age—have been debated for 20 years, based on data generated three to four decades ago. The controversy has continued largely because our current approach to screening assumes all women have the same risk for the same type of breast cancer. In fact, we now know that cancers vary tremendously in terms of timing of onset, rate of growth, and probability of metastasis. In an era of personalized medicine, we have the opportunity to investigate tailored screening based on a woman’s specific risk for a specific tumor type, generating new data that can inform best practices rather than to continue the rancorous debate. It is time to move from debate to wisdom by asking new questions and generating new knowledge. The WISDOM Study (Women Informed to Screen Depending On Measures of risk) is a pragmatic, adaptive, randomized clinical trial comparing a comprehensive risk-based, or personalized approach to traditional annual breast cancer screening. The multicenter trial will enroll 100,000 women, powered for a primary endpoint of non-inferiority with respect to the number of late stage cancers detected. The trial will determine whether screening based on personalized risk is as safe, less morbid, preferred by women, will facilitate prevention for those most likely to benefit, and adapt as we learn who is at risk for what kind of cancer. Funded by the Patient Centered Outcomes Research Institute, WISDOM is the product of a multi-year stakeholder engagement process that has brought together consumers, advocates, primary care physicians, specialists, policy makers, technology companies and payers to help break the deadlock in this debate and advance towards a new, dynamic approach to breast cancer screening.

Genome‐wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

“…This is supported by the demonstrated clinical utility of PRS for breast and prostate cancers, for which commercial panels are now available. Clinical trials to evaluate the ability of PRS to inform breast cancer screening recommendations are currently underway . We propose that similar utility could be gained by adding PRS to risk‐prediction methods for cutaneous malignancies, which may then be used to inform screening recommendations for high‐ and low‐risk individuals.…”

Performance of Single-Nucleotide Polymorphisms in Breast Cancer Risk Prediction Models: A Systematic Review and Meta-analysis

“…Breast cancer is the most common cancer among women and is rising in incidence worldwide (1,2). In this era of precision medicine, there is interest in applying tailored breast cancer screening and prevention strategies based on a woman's specific risk (3). Many risk factors have been identified and risk prediction models developed to quantify the combined effect of these factors (4).…”

Uptake of polygenic risk information among women at increased risk of breast cancer

“…Such frameworks will need to account for monogenic risk genes and other breast cancer risk factors such as family history and lifestyle. Studies assessing the different applications of PRS should also be conducted, including as a modifier of high-and moderate-risk breast cancer risk genes,36,37 and for population screening programs [38][39][40]. Each application of PRS will have its own unique set of research questions which will need to be investigated.Results should be interpreted in light of the study's strengths and limitations.…”