For decades, annual mammograms starting at age 40 have been treated as a standard rule. New research suggests that approach may not suit everyone. A large U.S. clinical trial found that most women prefer breast cancer screening schedules based on individual risk rather than age alone—and that doing so is just as safe.
The findings come from the WISDOM trial, coordinated by the University of California, San Francisco, and published on December 12 in JAMA. The study examined whether risk-based screening could match the safety of annual mammography while reducing unnecessary testing.
The trial enrolled 46,403 women aged 40 to 74 nationwide. Of these, 28,372 agreed to be randomly assigned to either annual mammograms or a personalized screening plan. The tailored plans were based on genetic testing, personal and family health history, lifestyle factors, and breast density.
Researchers focused on a key safety question: would fewer screenings for lower-risk women lead to more advanced cancers? The answer was no. Rates of stage 2B or higher breast cancers were not higher in the risk-based group than in the annual screening group.
In the personalized arm, women were assigned to different screening schedules based on risk. Those at lowest risk delayed screening until age 50 or until their risk increased. Women at highest risk—about 2% of participants—received the most intensive monitoring, alternating mammograms and MRIs every six months. Others followed biennial or annual schedules.
Notably, no advanced cancers were reported among women in the highest-risk group. Researchers say this highlights a gap in current guidelines, which may underserve women with elevated risk by placing them on average-risk screening schedules.
The trial relied on a digital platform. Genetic test kits were mailed to participants, and imaging results were uploaded electronically or sent directly from imaging centers.
“The personalized approach begins with risk assessment, incorporating genetic, biological, and lifestyle factors, which can then guide effective prevention strategies,” said Dr. Laura Esserman, director of the UCSF Breast Care Center and the study’s lead author.
The study did not meet one secondary goal: reducing biopsy rates. Overall biopsy numbers were similar in both groups. However, biopsies were more concentrated among women at higher risk, suggesting procedures were more targeted rather than broadly reduced.
Genetic testing revealed another key finding. Thirty percent of women who carried gene variants linked to higher breast cancer risk reported no family history of the disease. Under current guidelines, most would not have been offered genetic testing. The analysis included nine genes, such as BRCA1 and BRCA2, along with a polygenic risk score that measures cumulative genetic risk.
“When used as part of a comprehensive risk assessment, these results could have a real impact on improving the safety and effectiveness of screening and prevention,” said Allison Fiscalini, director of the Athena Breast Health Network and the WISDOM study.
Overall, the risk-based approach proved noninferior to annual screening, with a lower rate of advanced cancers by 18 cases per 100,000 person-years. For many women, the findings suggest that individualized screening may be a safe alternative—and a reason to rethink the need for yearly mammograms.
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