Breast cancer is a heterogeneous disease characterized by the uncontrolled growth of malignant cells in breast tissue, arising from a complex interplay of genetic, hormonal, environmental, and lifestyle factors. It is the most commonly diagnosed cancer among women worldwide, though it can also occur in men. Credit: Stock
New research indicates that personalized breast cancer screening based on individual risk could improve detection while reducing unnecessary testing.
A new study suggests that tailoring breast cancer screening to a person’s individual risk may be more effective than relying on routine annual mammograms for everyone. By focusing on personal risk factors, this approach can reduce the likelihood of detecting cancers at a more advanced stage while still ensuring that each person receives an appropriate level of screening.
The findings are based on data from 46,000 women in the United States who participated in the first phase of the WISDOM study. The results point to a shift away from screening strategies based solely on age and toward a model that begins with a thorough assessment of risk. This personalized evaluation can then be used to determine the most suitable screening schedule for each woman. UCSF served as the coordinating center for the research.
“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. Essermanis the first author of the study, published on December 12th 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 is the most commonly diagnosed cancer among women in the United States, aside from skin cancers. For many years, screening guidelines were built on the assumption that all women faced similar risk and were therefore driven largely by age. This approach persisted despite growing evidence showing that breast cancer risk can differ substantially from one individual to another.
How the WISDOM Study Works
WISDOM compared the standard annual mammogram with an approach based on individual risk. Women were stratified into four groups, based on their age, genetics, lifestyle, health history, and breast density, using well-validated risk models.
Those in the lowest risk category — 26% of the participants — were told not to screen until they reached age 50 or when an algorithm predicted their risk would meet the level of a 50-year-old. Those with average risk, who made up 62%, were told to screen every two years. Annual screening was recommended for the 8% of women with elevated risk. The 2% of women in the highest risk category received two screenings a year, alternating between mammography and MRI, regardless of their age.
Personalized Prevention and Patient Preferences
Those with either elevated or highest risk got personalized recommendations for how to reduce their risk of getting breast cancer. This included an online tool to make breast health decisions and direct outreach from a breast health specialist. The recommendations included ways to improve diet and exercise, as well as considerations for risk-reducing medications.
This risk-based screening approach did not result in an increase in the frequency of higher cancers. Participants who did not want to be randomized could still enroll in an observational group, where they could choose their own screening approach. Of these participants, 89% chose risk-based screening, showing that it was preferred by women.
“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 professor of Medicine at UCSF who develops and evaluates risk assessment tools for breast cancer.
Since its inception in 2016, WISDOM has enrolled more than 80,000 women. In recent years, researchers enrolled women as young as 30 to identify those who could be at risk of developing aggressive early cancers because of the pathogenic variants they carry.
Expanding the Role of Genetic Testing
Importantly, the study found that 30% of the women who tested positive for a genetic variant that increased their risk of breast cancer did not report a family history of breast cancer. Under current clinical guidelines, these people would not normally be offered genetic testing.
In addition to the more widely known pathogenic variants that increase risk for breast cancer — such as BRCA1 and BRCA2 — WISDOM also looked at other smaller changes in DNA that when taken together in a polygenic risk score can better predict risk. This made the prediction algorithm even more precise, shifting between 12% and 14% of the participants to a different level of risk.
“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.”
WISDOM is continuing to advance risk assessment through the WISDOM 2.0 study, which is now actively enrolling participants. The goal is to identify women at higher risk for developing more aggressive breast cancers, so they can be offered personalized screening and prevention options that may better support their long-term health.
Reference: “Risk-Based vs Annual Breast Cancer Screening: The WISDOM Randomized Clinical Trial” by Laura J. Esserman, Allison S. Fiscalini, Arash Naeim, Laura J. van‘t Veer, Andrea Kaster, Maren T.
Scheuner, Andrea Z. LaCroix, Alexander D. Borowsky, Hoda Anton-Culver, Olufunmilayo I. Olopade, James Esserman, Rachael Lancaster, Lisa Madlensky, Amie M.
Blanco, Katherine S. Ross, Deborah L. Goodman, Barry S. Tong, Michael Hogarth, Diane Heditsian, Susie Brain, Vivian Lee, Kelly Blum, Mi-Ok Kim, Leah P.
Sabacan, Kirkpatrick B. Fergus, Christina Yau, Hannah L. Park, Barbara A. Parker, Celia Kaplan, Kim F.
Rhoads, Suzanne Eder, Kelly Adduci, Jeffrey B. Matthews, Neil S. Wenger, Yiwey Shieh, Robert A. Hiatt, Elad Ziv, Jeffrey A.
Tice and Martin Eklund, 12 December 2025, JAMA.
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.
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