Genetic Testing Improves Comprehensive Risk-Based Screening for Breast Cancer

This one-size-fits-all approach can lead to over-screening in low-risk women and missed opportunities for prevention and early detection in those at higher risk. A large U.S. study now shows that tailoring screening schedules based on a comprehensive assessment of personal risk can reduce the likelihood of more advanced cancers while safely matching women to the level of screening they actually need.

The study was coordinated by the University of California, San Francisco (UCSF, San Francisco, CA, USA) as part of the WISDOM (Women Informed to Screen Depending on Measures of risk) study. Instead of assigning annual mammograms based solely on age, the approach begins with a detailed risk assessment incorporating genetics, breast density, medical history, lifestyle factors, and validated risk models. Women are then assigned personalized screening intervals and prevention strategies aligned with their individual risk.

Participants were stratified into four risk categories. Women at lowest risk were advised to delay screening until age 50 or until their predicted risk increased, while those at average risk were screened every two years. Annual mammography was recommended for women with elevated risk, and those at the highest risk received twice-yearly screening alternating between mammography and MRI, regardless of age. Higher-risk participants also received tailored guidance on risk reduction, including lifestyle changes and consideration of preventive medications.

The first phase of the WISDOM study enrolled 46,000 women across the United States. Results showed that risk-based screening did not increase the incidence of later-stage breast cancers compared with annual mammography. Importantly, women strongly preferred the personalized approach, with nearly 90% of those given a choice opting for risk-based screening. The findings were published in JAMA and demonstrate that individualized screening can be both safe and effective at a population level.

The study also revealed that 30% of women carrying high-risk genetic variants had no family history of breast cancer and would not have qualified for genetic testing under current guidelines. By combining testing for high-impact mutations with polygenic risk scores, the model refined risk estimates and reassigned up to 14% of participants to more appropriate screening categories. Ongoing work through WISDOM 2.0 aims to further improve early identification of women at risk for aggressive cancers and expand personalized prevention strategies.

“These findings should transform clinical guidelines for breast cancer screening and alter clinical practice,” said Laura J. Esserman, MD, MBA, first author of the study. “The personalized approach begins with risk assessment, incorporating genetic, biological, and lifestyle factors, which can then guide effective prevention strategies.”

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