Risk-stratified breast cancer screening - a protocol for a non-blinded randomised trial

Breast cancer accounts for 14% of all cancer-related deaths among women. Women aged 50-69 years are offered biennial mammography, which reduces breast cancer-specific mortality. Simulations suggest that risk-stratified screening detects more early-stage cancers while lowering the number of unnecessary recalls, assessments and biopsies in low-risk women. This trial will investigate whether multifactorial risk-stratified screening, including polygenic score, is feasible, acceptable, cost-efficient and safe.

A minimum of 962 consenting women aged 50-67 years will be randomised 1:1 into a control group receiving standard screening or an intervention group offered screening intervals based on individual risk. Risk factor data collection, communication and follow-up will occur online using a tool co-designed with women in the target group. The primary outcome will be the proportion of low-risk women who, within 800 days of their baseline mammogram, will refrain from their legally ensured two-year mammogram interval. Secondary outcomes include quality of life, anxiety and breast cancer worry, measured at baseline and repeated three times during follow-up. In addition, health economy analyses will be conducted.

The findings will inform the development of large-scale risk-stratified screening trials.

Novo Nordisk Foundation, grant no. NNF21OC0070842. ACA is supported by Cancer Research UK grants: PPRPGM-Nov20\100002 and SEBCD3-2024/100001.

gov Identifier: NCT06060938. Registration date: 11092023.