WISDOM Study Finds Personalized Breast Screening Viable For Some Women

On December 12, 2025, investigators published initial results from the Women Informed to Screen Depending on Measures of Risk study in JAMA and presented the findings at the San Antonio Breast Cancer Symposium. The trial, launched in 2016 under the direction of Dr. Laura Esserman at UCSF and the Athena Network, enrolled more than 28,000 women aged 40 to 74 for the first reported analysis and compared a risk based, individualized screening strategy to the U.S. standard of annual mammography.

Participants in the personalized arm were assigned by an algorithm to one of four screening regimens based on a composite risk profile that included age, breast density, personal and family history, and genetic information. Women in that arm were offered optional testing of nine genes associated with markedly elevated breast cancer risk, BRCA1, BRCA2, ATM, TP53 sometimes reported as P53, PTEN, CHEK2, CDH1, PALB2 and STK11. The trial also evaluated 120 single nucleotide polymorphisms to calculate polygenic risk scores, reflecting the growing evidence that many small genetic effects can add predictive value when combined with other markers.

Investigators report that differing regimens for higher and lower risk women performed "as good as" annual screening in the cohort described, and that the risk based approach permitted de intensification of screening for some lower risk women and escalation for higher risk women without apparent loss of effectiveness so far. All participants received counseling and the study team piloted a low literacy, visual risk communication tool that integrates genetic, polygenic and lifestyle factors and quantifies the risk reduction potential of medications and behavior change.

WISDOM is assembling a large, curated dataset of clinical screening results, imaging and biospecimens intended to support future personalized screening strategies. The study is the U.S. companion to the international MyPeBS trial and was supported by a Patient Centered Outcomes Research Institute grant awarded to Athena in 2015. Source documents also reference related initiatives including the TMIST imaging trial, underscoring parallel efforts to build research databases that could refine screening for diverse populations.

Public health specialists welcomed the prospect of tailoring screening to individual risk as a way to reduce unnecessary imaging and the anxiety, biopsies and overtreatment that can follow false positives and detection of low grade lesions. The WISDOM results were presented in the context of other shifting evidence. Earlier this year, the COMET trial found that for some women with ductal carcinoma in situ careful monitoring with more frequent imaging did not raise subsequent cancer risk compared with immediate surgery and radiation.

Yet significant questions remain before guidelines change. The reported results are from an initial cohort, longer follow up is needed to assess interval cancers and mortality outcomes, and source documents note some operational inconsistencies in broader program materials. Equity and access are central concerns. Personalized screening depends on access to genetic testing, counseling and high quality data, and without deliberate policies and investment there is a risk of widening disparities for women of color, rural communities and those with limited resources.

For clinicians and policymakers, WISDOM adds important evidence that one size does not fit all. Translating these findings into practice will require guideline endorsement, insurer and government coverage decisions, expanded genetic counseling capacity, protections for genetic data, and continued efforts to recruit and represent diverse participants in studies that will shape the next generation of screening policy.