Risk-based screening reclassifies mammography recommendations for Asian women

A prospective Singapore cohort and two breast cancer case cohorts examined screening recommendations based on polygenic and classical risk factors in 9,761 Asian women. Among women aged 40–49, the approach assigned many to less frequent or no screening, but prospective cancer events were limited and some cancers missed by the polygenic score had more aggressive features.

Combined risk factors captured 68–69% of cases in case cohorts.
Nearly 39% of eligible women aged 40–49 were assigned no screening.
Only 41 subsequent cancers occurred in the prospective cohort.
PRS-missed cancers had several features associated with more aggressive disease.

The BREATHE multicentre prospective cohort enrolled 4,513 women aged 35–59 years at six Singapore sites between 2021 and 2023. Researchers assessed screening recommendations using a five-year absolute-risk threshold, a 313-variant polygenic risk score (PRS), the Gail model and additional factors. They also evaluated case capture in two retrospective cohorts: the Singapore Breast Cancer Cohort (2,782 cases) and the Malaysian Breast Cancer Genetic Study (2,466 cases), for a combined 9,761 participants across the analyses.

Among 2,003 healthy women aged 40–49 who would be recommended annual mammography under Singapore guidance, 776 (38.7%) were assigned no screening and 960 (47.9%) biennial screening. Of 41 cancers diagnosed after BREATHE enrolment, 35 (85.4%) occurred in women classified as screening-eligible at baseline. In the two case cohorts, combining PRS and Gail-model risk captured 68–69% of cases aged 40–49, compared with about 54% for PRS alone. PRS-missed cases were more likely to have progesterone receptor-negative tumours, tumours at least 50 mm, and germline protein-truncating variants in predisposition genes.

The findings suggest potential to tailor screening, but do not establish that changing screening intervals is safe or improves outcomes. The prospective cohort had only 41 subsequent cancer diagnoses; the authors call for evaluation in larger prospective studies. The analysis also used retrospective case cohorts for comparative case capture, rather than a prospective comparison of screening strategies.

In practice

This study does not justify changing mammography practice. It suggests that combining PRS with the Gail model and other risk indicators could identify different screening groups among Asian women, including women aged 40–49 who might otherwise receive annual mammography under Singapore guidance. However, the prospective cohort recorded only 41 subsequent cancers, and the comparisons relied partly on retrospective case cohorts. Larger prospective studies are needed to establish the safety and effectiveness of risk-adapted screening before applying these reclassifications clinically.

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Source

BMC Medicine: Polygenic and classical risk integration reshapes breast cancer screening recommendations in 9,761 Asian women ↗

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