A Major Study Shows How Personalized Breast Cancer Screening Could Replace Annual Mammograms
A large new U.S. study suggests there may be a smarter and more precise way to screen for breast cancer than the long-standing “one-size-fits-all” approach of annual mammograms. Instead of relying mainly on age, researchers found that personalized, risk-based screening can safely match women to the amount and type of screening they actually need — while reducing the chances of detecting cancer at a more advanced stage.
The findings come from the WISDOM study, one of the largest breast cancer screening trials ever conducted in the United States. Coordinated by the University of California, San Francisco (UCSF), the study followed tens of thousands of women and compared traditional annual mammography with an individualized screening strategy based on each woman’s personal risk.
Why the Traditional Screening Model Is Being Questioned
Breast cancer remains the most common cancer among women in the U.S., excluding skin cancer. For decades, screening guidelines have largely assumed that most women share similar levels of risk, leading to recommendations based mainly on age. Typically, this has meant annual mammograms starting at age 40 or 50, depending on the guideline.
However, research has consistently shown that breast cancer risk varies widely from person to person. Genetics, breast density, lifestyle, reproductive history, and overall health all play important roles. Despite this, screening recommendations have been slow to fully reflect these differences.
The WISDOM study was designed to test whether a risk-based screening approach could offer a safer and more effective alternative.
How the WISDOM Study Was Designed
The first phase of the WISDOM study included 46,000 women across the United States, making it one of the most comprehensive breast cancer screening trials to date. Participants were either randomly assigned to annual mammography or to a screening plan tailored to their individual risk.
Instead of relying on age alone, the personalized approach used well-validated risk models that incorporated:
- Genetic information, including high-risk mutations
- Polygenic risk scores, which assess many small DNA changes together
- Breast density, known to affect cancer risk and detection
- Lifestyle factors, such as physical activity
- Medical and reproductive history
Based on these factors, women were placed into four distinct risk categories, each with its own screening recommendation.
The Four Risk Groups and Their Screening Plans
The study’s personalized model carefully matched screening intensity to risk level:
- Lowest risk group (26% of participants): These women were advised not to begin screening until age 50, or until their calculated risk reached the equivalent of a typical 50-year-old.
- Average risk group (62%): Screening every two years was recommended.
- Elevated risk group (8%): These women were advised to undergo annual mammograms.
- Highest risk group (2%): Women in this category received two screenings per year, alternating between mammography and MRI, regardless of age.
In addition to screening, women in the elevated and highest risk groups were offered personalized prevention guidance, including lifestyle changes and discussions around risk-reducing medications.
What the Study Found
One of the biggest concerns with reducing screening frequency for lower-risk women is the possibility of missing aggressive cancers. The WISDOM study directly addressed this issue.
The results showed that risk-based screening did not increase the rate of advanced breast cancers compared with annual mammography. In fact, the number of higher-stage cancers detected was similar — and in some analyses slightly lower — in the personalized screening group.
This demonstrated that less frequent screening for low-risk women did not compromise safety, while higher-risk women received more intensive monitoring.
Women Preferred the Personalized Approach
The study also included an observational group of women who chose their own screening strategy rather than being randomized. Among these participants, an overwhelming 89% opted for risk-based screening.
This strong preference suggests that many women are comfortable moving away from rigid annual screening schedules when given clear, individualized information about their risk.
The Crucial Role of Genetics
One of the most striking findings from the study involved genetic testing. About 30% of women who carried a genetic variant associated with higher breast cancer risk reported no family history of the disease.
Under current clinical guidelines, these women typically would not qualify for genetic testing. This means many high-risk individuals could be missed entirely using today’s standard screening framework.
Beyond well-known genes like BRCA1 and BRCA2, the study also evaluated smaller genetic variations combined into polygenic risk scores. This more detailed genetic analysis shifted 12% to 14% of participants into different risk categories, further refining screening recommendations.
Why Risk-Based Screening Matters for the Healthcare System
Personalized screening has implications beyond individual patients. By reducing unnecessary mammograms for low-risk women and focusing resources on higher-risk individuals, healthcare systems can potentially improve outcomes while using resources more efficiently.
This approach could also help reduce false positives, unnecessary biopsies, anxiety, and overdiagnosis — long-standing concerns associated with routine annual screening.
What Comes Next: WISDOM 2.0
The research team is now moving forward with WISDOM 2.0, which aims to further improve risk prediction, especially for aggressive and early-onset breast cancers. The updated study is enrolling women as young as 30, allowing researchers to identify high-risk individuals much earlier.
The long-term goal is to build a screening system that adapts as science advances — one that continuously updates risk assessments as new genetic and clinical data become available.
Understanding Breast Cancer Risk Beyond Age
This study highlights an important shift in how breast cancer risk is understood. Age alone is a blunt tool for predicting risk. Two women of the same age can have vastly different chances of developing breast cancer, depending on genetics, breast density, and lifestyle factors.
As precision medicine continues to evolve, screening strategies like the one tested in WISDOM could become the foundation for future clinical guidelines, offering safer, more effective, and more personalized care.
Final Thoughts
The WISDOM study provides strong evidence that personalized, risk-based breast cancer screening works — and works safely. While more research and policy discussions are needed before guidelines change, this study marks a major step toward a more individualized approach to women’s health.
If adopted more widely, risk-based screening could reshape how breast cancer is detected and prevented, ensuring that each woman receives the right level of care at the right time.
Research paper:
https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2025.24784
