A smarter way to screen for breast cancer is emerging

The findings are based on data from 46,000 women across the United States who took part in the first phase of the WISDOM study. The results point to a major change in how breast cancer screening could be approached, moving away from age-based rules and toward a system built around comprehensive risk evaluation. UCSF served as the coordinating center for the study.

Why Age Alone May Not Be Enough

"These findings should transform clinical guidelines for breast cancer screening and alter clinical practice," said Laura J. Esserman, MD, MBA, director of the UCSF Breast Care Center. Esserman is the study's first author. The research was published Dec. 12 in JAMA and presented at the San Antonio Breast Cancer Symposium. "The personalized approach begins with risk assessment, incorporating genetic, biological, and lifestyle factors, which can then guide effective prevention strategies."

Breast cancer remains the most commonly diagnosed cancer among women in the United States, excluding skin cancers. For decades, screening guidelines assumed that most women faced similar risk and relied largely on age as the deciding factor, even though research has long shown that breast cancer risk can vary greatly from one person to another.

How the WISDOM Study Worked

The WISDOM study directly compared traditional annual mammography with a screening strategy based on individual risk. Using well validated risk models, researchers grouped participants into four categories by considering age, genetic information, lifestyle factors, health history, and breast density.

Women in the lowest risk group, representing 26% of participants, were advised to delay screening until age 50 or until an algorithm indicated their risk had reached that of a typical 50-year-old. Those at average risk, about 62% of the group, were advised to undergo screening every two years. Annual mammograms were recommended for the 8% classified as having elevated risk. The highest risk group, accounting for 2% of participants, was advised to receive screening twice a year, alternating between mammography and MRI, regardless of age.

Personalized Prevention for Higher-Risk Women

Participants identified as having elevated or highest risk also received customized guidance on lowering their chances of developing breast cancer. Support included access to an online decision-making tool focused on breast health and direct contact with a breast health specialist. Recommendations covered lifestyle changes such as improving diet and increasing physical activity, along with discussions about medications that can help reduce risk.

Importantly, the personalized screening approach did not lead to a higher rate of late-stage cancer diagnoses. Women who chose not to be randomized were able to join an observational group and select their preferred screening strategy. Among them, 89% opted for risk-based screening, suggesting strong acceptance of the personalized approach.

"Shifting resources from lower-risk women to higher-risk women is an efficient, effective approach to screening for and preventing breast cancer," said co-author Jeffrey A. Tice, MD, a UCSF professor of Medicine who specializes in developing and evaluating breast cancer risk assessment tools.

Expanding Genetic Testing Beyond Family History

Since launching in 2016, WISDOM has enrolled more than 80,000 women. More recently, researchers have included women as young as 30 in an effort to identify those who may face an increased risk of aggressive early cancers due to inherited genetic variants.

One of the study's most notable findings was that 30% of women who tested positive for a genetic variant linked to higher breast cancer risk reported no family history of the disease. Under current clinical guidelines, many of these women would not typically qualify for genetic testing.

In addition to well known pathogenic variants such as BRCA1 and BRCA2, the study also evaluated smaller DNA changes that can be combined into a polygenic risk score. This approach improved the precision of risk predictions and resulted in 12% to 14% of participants being reassigned to a different risk category.

"This is one of the first studies to offer genetic testing to all women, regardless of family history," said co-author Allison S. Fiscalini, MPH, of UCSF, director of the Athena Breast Health Network and the WISDOM study. "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."

What Comes Next for Risk-Based Screening

Researchers are continuing to refine risk assessment through the WISDOM 2.0 study, which is now enrolling participants. The goal is to better identify women who face a higher likelihood of developing aggressive breast cancers and provide them with screening and prevention strategies tailored to their long-term health needs.

Co-Authors: From UCSF, authors include Laura J. van 't Veer, PhD; Maren T. Scheuner MD; Alexander D. Borowsky, MD; Amie M. Blanco, MD; Katherine S. Ross, MS; Barry S. Tong, MS; Diane Heditsian; Susie Brain; Vivian Lee; Kelly Blum, MS; Mi-Ok Kim, PhD; Leah P. Sabacan, MBA; Kirkpatrick B. Fergus, MD; Christina Yau, PhD; Celia Kaplan, DrPH; Suzanne Elder, CFNP; Kelly Adduci, MPH; Jeffrey B. Matthews, PhD; Robert A. Hiatt, MD, PhD; Elad Ziv, MD; and Jeffrey A. Tice, MD.

Other investigators are at UC Los Angeles; UC Irvine; UC San Diego; San Francisco VA Health Care System; Sanford Health in North Dakota; University of Chicago; Diagnostic Center of Miami; University of Alabama; Virginia Commonwealth University; Weill Cornell Medicine in New York; and the Karolinka Institutet in Stockholm.

Funding: Study support included the Patient Center Outcomes Research Institute, the National Cancer Institute (R01CA237533), and the Breast Cancer Research Foundation. Please see the paper for other funding sources.

Conflicts of Interest: Esserman is a medical advisory panel member for Blue Cross Blue Shield and has receive author fees from the UpToDate electronic medical information resource. Please see the paper for disclosures of other investigators.