Top Line: Can we finally bring the sophistication of individualized prostate cancer screening to breasts?
The Study: Despite risk stratification tools galore, breast screening guidelines have remained woefully unidimensional for decades. The WISDOM trial randomized >28K women aged 40–74 to risk-based screening versus standard annual mammography. Risk stratification incorporated clinical factors, breast density, polygenic risk scores, and pathogenic variants in nine susceptibility genes. You may be wondering: how do I know if a woman has pathogenic variants..? Apparently all women regardless of family history in the risk-based arm–but not standard arm–underwent testing for pathogenic or likely pathogenic variants in 9 breast cancer susceptibility genes (including BRCA1, BRCA2, PALB2, CHEK2, ATM, among others) via mailorder home-testing kits. With this information in hand, women in the risk-based arm were then assigned to screening intensities ranging from q6-month breast MRI/mammography (2%) to initiating yearly mammography at age 40 (8%) to no screening before age 50 and only every-other-year thereafter (everyone else). After a median follow-up of over 5 years, the primary endpoint of diagnoses of stage ≥II cancers was noninferior with risk-based screening. Despite substantially fewer mammograms overall in the risk based group, biopsy rates unfortunately were not reduced. This was due to a heavy skew towards the 2% of women at highest risk in the risk-based arm–receiving yearly breast MRI and MMG–who received over half of all biopsies performed.
TBL: The WISDOM study suggests, using clinical risk calculators paired with universal genetic testing, the vast majority of women can safely de-escalate mammogram screening to every other year starting only at age 50. | Esserman, JAMA 2025
The Study: Despite risk stratification tools galore, breast screening guidelines have remained woefully unidimensional for decades. The WISDOM trial randomized >28K women aged 40–74 to risk-based screening versus standard annual mammography. Risk stratification incorporated clinical factors, breast density, polygenic risk scores, and pathogenic variants in nine susceptibility genes. You may be wondering: how do I know if a woman has pathogenic variants..? Apparently all women regardless of family history in the risk-based arm–but not standard arm–underwent testing for pathogenic or likely pathogenic variants in 9 breast cancer susceptibility genes (including BRCA1, BRCA2, PALB2, CHEK2, ATM, among others) via mailorder home-testing kits. With this information in hand, women in the risk-based arm were then assigned to screening intensities ranging from q6-month breast MRI/mammography (2%) to initiating yearly mammography at age 40 (8%) to no screening before age 50 and only every-other-year thereafter (everyone else). After a median follow-up of over 5 years, the primary endpoint of diagnoses of stage ≥II cancers was noninferior with risk-based screening. Despite substantially fewer mammograms overall in the risk based group, biopsy rates unfortunately were not reduced. This was due to a heavy skew towards the 2% of women at highest risk in the risk-based arm–receiving yearly breast MRI and MMG–who received over half of all biopsies performed.
TBL: The WISDOM study suggests, using clinical risk calculators paired with universal genetic testing, the vast majority of women can safely de-escalate mammogram screening to every other year starting only at age 50. | Esserman, JAMA 2025