Risk-Based Mammography (With Most Women Getting Biennial Screening Starting at Age 50 Years) Is Noninferior to Annual Screening

Is risk-based mammography noninferior to routine annual screening in women aged 40 to 74 years?

A risk-based mammography strategy is noninferior to annual screening, with a trend toward fewer high-grade cancers but also more biopsies. Of note, most women in the risk-based group (12,512 out of 14,212) had biennial mammography starting at age 50 years; most women in the comparison group had annual mammography starting at 40 years. More follow-up is needed to clarify the impact on mortality. (Level of Evidence = 1b−)

The only guidelines in the world recommending annual mammography come from US specialty societies (American College of Radiology and American College of Obstetricians and Gynecologists). Other societies recommend biennial mammography. However, these one-size-fits-all recommendations ignore large differences in risk based on genetics and breast density. The researchers randomized 28,372 women to receive routine annual mammography or risk-based screening in four risk groups (according to the Breast Cancer Surveillance Consortium risk model that incorporated a polygenic risk score based on 75–126 single nucleotide variants): group 1 (highest risk; n = 291) received alternating magnetic resonance imaging (MRI) and mammography every 6 months; group 2 (high risk; n = 1,121) received annual mammography starting at age 40 years; group 3 (average risk; n = 8,796) received biennial mammography starting at age 50 years; and group 4 (low risk [ie, younger than 50 years with a 5-year risk of less than 1.3%]; n = 3,716) also began biennial mammography at age 50 years.

Women with a history of breast cancer or ductal carcinoma in situ (DCIS) were excluded. At baseline, groups were similar with a good distribution by age; only 3% had a pathogenic genetic variant, including 1% with a high-risk pathogenic variant. The participants were largely White and well-educated, which may limit generalizability. After a median 5 years of follow-up, the primary outcome of the number of stage IIB or more advanced cancers was numerically lower in the risk-based screening group (30 vs 48 cancers per 100,000 person-years; 95% CI for the risk difference, −40.2 to 4.1). The other coprimary outcome was the rate of biopsies, which was higher in the risk-based group, but this difference was not statistically significant (1,371 vs 1,272 biopsies per 100,000 person-years; 95% CI for the risk difference, −18 to 215). The overall number of cancers and DCIS detected were nearly identical between groups. Of 523 cancers detected in the risk-based mammography and routine annual screening groups, about 10% were detected because of symptoms. There were significantly more MRIs in the risk-based group (1,187 vs 795 per 100,000 person-years) but fewer mammograms (43,084 vs 46,919 per 100,000 person-years).

Study design: Randomized controlled trial (nonblinded)

Funding source: Government and foundation

Allocation: Uncertain

Setting: Outpatient (any)

Reference: Esserman LJ, Fiscalini AS, Naeim A, et al. Risk-based vs annual breast cancer screening: the WISDOM randomized clinical trial. JAMA. 2026; 335(9): 763-774.

Editor’s Note: Dr. Ebell is cofounder and editor-in-chief of Essential Evidence Plus.