5-Year Absolute Risk–Based Breast Cancer Screening Could Save More Lives, Reduce False Alarms

Tailoring mammography screening to a woman's individual breast cancer risk, rather than age alone as current guidelines suggest, could prevent more deaths while also significantly reducing the burden of false-positive results, a study published in JAMA Network Open suggests.¹

The study used 2 independently developed computer simulation models to compare 47 risk-based screening strategies against the standard age-based approaches currently recommended by major medical organizations. The US Preventative Services Task Force (USPSTF) for instance, recommends biennial screening for all women aged 40 to 74.² Nine of the risk-based strategies performed as well as or better than the current benchmark on both measures at once: lives saved and false alarms avoided.

Rather than relying solely on age as the trigger for mammography, risk-based screening uses a validated calculator to estimate each woman's 5-year probability of developing invasive breast cancer. Factors like breast density, family history, prior biopsy results, race, ethnicity, and menopausal status all feed into the calculation. Women are then sorted into low-, average-, intermediate-, or high-risk categories, each assigned a different screening frequency. Crucially, a woman's risk is reassessed every 5 years as she ages, meaning the strategy adapts over time.

The risk calculator used in the study has been available for over 17 years, developed from data on 1.5 million US women. However, a limitation of the study is that it relied on computer simulation rather than real-world trial data. The risk calculator used also does not yet incorporate genetic factors like polygenic risk scores.

Under one of the best-performing strategies, women at low risk would skip or delay screening while women at high risk would get scanned more frequently starting at younger ages. Compared with the standard biennial screening from 40 to 74, the risk-focused approach was associated with 6% more breast cancer deaths prevented (7.2 per 1000 women compared with 6.8) and 13% fewer false-positive recalls per 1000 women.

Another strategy that began risk assessment at age 50 rather than 40 did even better on deaths prevented, projecting a 10% improvement while also producing 10% fewer false positives.

Across all 9 top-performing risk-based strategies, false-positive recalls dropped by 8% to 23% compared with the standard approach. This reduction is meaningful to patients, as false positives can trigger anxiety as well as additional imaging and unnecessary biopsies.

The authors stated that, “by shifting the focus from uniform population-wide recommendations based on age alone to individualized risk-based strategies, these approaches were projected to maintain or improve mortality benefits while reducing the burden of screening harms.”

In practice, a risk-based approach would mean that women classified as low risk would undergo less frequent or no screening in their 40s and early 50s, reducing their exposure to false positives and unnecessary procedures. Women at intermediate or high risk would be screened more intensively, often annually, at younger ages than current guidelines typically recommend.

Women at the very highest risk, for instance, those with BRCA1/2 gene variants, a history of chest radiation, or prior breast cancer, were not included in this analysis, as they are already covered by separate high-risk guidelines recommending supplemental MRI screening.

The debate over who should get mammograms, how often, and starting at what age has been contentious for years. The USPSTF updated its guidelines in 2024 to recommend biennial screening starting at 40, while the American College of Radiology recommends annual screening from 40, and the American College of Physicians recommends biennial screening beginning at 50. This study suggests that what matters more than the age-versus-frequency debate is whether the right women are being screened at the right intervals based on their actual risk.

Overall, the findings suggest that a shift away from one-size-fits-all mammography toward personalized screening schedules could save more lives with less collateral harm by screening more aggressively where it matters most and pulling back where the benefit is marginal.

“By shifting the focus from uniform population-wide recommendations based on age alone to individualized risk-based strategies, these approaches were projected to maintain or improve mortality benefits while reducing the burden of screening harms,” the authors concluded. “As personalized medicine advances, risk-based screening is poised to become a cornerstone of breast cancer prevention, offering a more nuanced and tailored approach to patient care.”

References

1. Alagoz O, Lu Y, Gil Quessep E, et al. Five-year absolute risk-based and age-based breast cancer screening in the US. JAMA Netw Open. 2026;9(1):e2552944. doi:10.1001/jamanetworkopen.2025.52944

2. Breast cancer: screening. United States Preventive Services Taskforce. April 30, 2024. Accessed March 2, 2026. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening