Is Risk-based Screening Justified by the WISDOM Trial?

Abstract Widespread mammography screening has resulted in a significant decline in breast cancer deaths, but it is resource intensive. The WISDOM (Women Informed to Screen Depending on Measures of Risk) trial attempts to assess screening based on individual risk as an alternative to age-based screening (annual screening starting at age 40 years). In their initial report, the authors concluded that risk-based screening is safe and acceptable. Their results do not support this conclusion. The first primary endpoint to test the noninferiority of risk-based screening used the metric of stage IIB and higher breast cancers. Many of these cancers would be apparent on physical exam, thus eliminating some advantages of early detection and ignoring shortcomings of the risk-based approach. In addition, the study set an extremely weak noninferiority margin, compromising their conclusion concerning noninferiority. Details of mammography and MRI use in WISDOM reflect poor compliance with screening protocols in both arms of the study. Substantial non-compliance as well as out-of-study imaging in both cohorts resulted in two nearly identical protocols, rather than a comparison of different screening strategies. The study’s findings of substantial non-compliance to the risk-based protocol make it difficult to justify risk-based screening being acceptable to women. The trial’s second primary endpoint, to test whether risk-based screening yielded fewer biopsies than annual screening, failed. The risk-based screening protocol is labor intensive and would be challenging to implement in the typical primary care practice. The vast majority of breast cancers occur in average-risk women and could be missed in a risk-based system, especially in women under age 50 and minority women.