A gene-based risk rule would thin out mammograms in the 40s

On 30 October 2026 the journal BMC Medicine published a Singapore study that asked whether every woman in her forties needs the same mammogram schedule. The BREATHE study enrolled 4,513 women aged 35 to 59 at six clinics in Singapore between 2021 and 2023 and, for each of them, estimated the five-year risk of breast cancer in two ways. One was a polygenic risk score, a single number that adds up the small effects of 313 common DNA variants read from a DNA sample. The other was the Gail model, a questionnaire-based calculator that uses age at first period, age at first birth, previous breast biopsies and breast cancer in a mother, sister or daughter.

Who would screen less, and who more

In Singapore, women aged 40 to 49 at average risk are advised to have a mammogram every year. The researchers applied a risk rule adapted from the US WISDOM trial: screening was recommended if either the genetic score or the Gail model put a woman's five-year risk at 0.9% or higher, roughly the risk of an average 50-year-old Singaporean woman, or if she had other markers such as extremely dense breasts. Among the 2,003 women in their forties, this rule would have moved 776 (38.7%) to no routine screening and 960 (47.9%) to a mammogram every two years. Only 262 (13.1%) would have kept the annual schedule, and 5 would have been moved up to annual mammography plus extra imaging. In the 50–59 group most women kept the standard two-year interval, while 160 (8.6%) were moved to yearly mammograms and 22 (1.2%) to yearly mammograms plus extra imaging. These were calculated recommendations compared with the current rules, not a measurement of what happened when care changed.

Where the women who later got cancer would have landed

Since enrolment, 41 of the women have been diagnosed with breast cancer; 35 of them (85%) would have been assigned at baseline to a category for which screening was recommended. In the forties group there were 19 such cancers, and the picture is mixed: 3 occurred in women the rule would have taken off screening and 11 in women it would have moved to two-yearly mammograms. To test the approach on more cases, the team applied the genetic score and the Gail model to two larger groups of women who already had breast cancer, 2,782 in Singapore and 2,466 in Malaysia; breast density and earlier recalls were not available there, so only these two estimates were used. Among women diagnosed at 40–49 (1,184 in Singapore and 1,122 in Malaysia), the two estimates together would have classed 69.1% and 67.8% as screening-eligible. The genetic score alone reached about 54%, and the questionnaire alone 37.2% and 32.9%.

What the tumours below the genetic threshold had in common

Women whose cancers fell below the genetic-score threshold were not a random sample. Among 1,931 invasive cancers diagnosed at 40–49 in the Singapore and Malaysian case groups, those below the threshold, compared with cancers that met the genetic criterion, were more often progesterone-receptor-negative, more often 5 cm or larger at diagnosis, and more often came with an inherited protein-truncating variant in one of nine predisposition genes, such as BRCA1, BRCA2 or PALB2; tumour grade, stage and lymph-node involvement did not differ. The authors suggest that a polygenic score, built from common variants, may preferentially flag women prone to slower-growing tumours that screening tends to find, while rare high-risk variants need separate genetic testing; they also name other possible explanations, including how well the score transfers across ancestries. They suggest that pairing the score with testing for these rare variants could catch more cancers than either approach alone, but they did not test that combination.

Reclassifying women is not the same as better outcomes

This is an observational analysis of how women would be reclassified, not a trial of outcomes. It does not show whether risk-based screening finds cancers earlier, causes fewer false alarms or saves lives; only 41 cancers have been diagnosed in the cohort so far, too few for firm conclusions about any age group. The comparison groups lacked data on breast density and earlier recalls, the 0.9% threshold was chosen rather than optimised, women joined by convenience sampling, and, as the authors note, most risk models and screening frameworks have been developed and validated mainly in populations of European ancestry. The study was funded by the JurongHealth Fund, Singapore's Agency for Science, Technology and Research and the PRECISE clinical implementation pilot fund, and the authors declare no competing interests. They conclude that randomised trials with long-term follow-up are needed before risk-based screening could replace age-based recommendations; the US WISDOM trial, whose framework the authors adapted, was designed as such a randomised comparison of risk-based and annual screening.

For now the study shows what a genetic score can and cannot add: in these cohorts it assigned women to screening categories more consistently than the questionnaire, but cancers below its threshold more often had features linked to more aggressive disease, and it says nothing about rare high-risk variants. If breast cancer runs in your family or you are unsure when to start or how often to have mammograms, discuss with your doctor whether a formal risk assessment or genetic counselling makes sense for you.

This material is for information only and does not replace a consultation with a doctor.

Sources

• Li J, Lim NST, Chin CH, et al. Polygenic and classical risk integration reshapes breast cancer screening recommendations in 9,761 Asian women. BMC Medicine. 2026;24:599. PMID 42963548 · DOI 10.1186/s12916-026-05334-5