Excess weight and unhealthy behaviours (sedentariness, high alcohol and suboptimal diet) are common among women attending breast screening. These factors increase the risk of breast cancer and other diseases. We tested the feasibility and acceptability of a weight loss/ behaviour change programme framed to reduce breast cancer risk (breast cancer prevention programme, BCPP) compared to one framed to reduce risk of breast cancer, cardiovascular disease (CVD) and diabetes (T2D) (multiple disease prevention programme, MDPP). Methods Women aged 47-73 years with overweight or obesity (n=1356) in the NHS Breast Screening Programme (NHSBSP) were randomized (1:2) to be invited to join a BCPP or a MDPP. The BCPP included personalised information on individual level of breast cancer risk and a web and phone weight loss/behaviour change intervention. The MDPP also included an NHS Health Check (lipids, blood pressure, HbA1c and personalised feedback for risk of CVD [QRISK2] and T2D [QDiabetes and HbA1c]). Uptake, retention, change in weight, and potential harms (anxiety and self-rated health) were assessed, along with the numbers in the MDPP with previously unknown CVD and T2D risk.ResultsThe BCPP and MDPP had comparable rates of uptake; 45/508 (9%) vs. 81/848 (10%) 12-month retention; 33/45 (73%) vs. 53/81 (65%) and numbers (%) losing ≥5% body weight at 12 months; 26/45 (58%) vs. 46/81 (57%) with baseline observation carried forward imputation. Both groups experienced reductions in state anxiety score; BCPP (n=37) -0.7 (-4.6 to 3.2), MDPP (n=60) -3.5 (-6.7 to -0.4) and an increase in the EQ-5D-5L score; BCPP (n=40) 4.1 (0.6 to 7.6), MDPP (n=60) 7.3 (3.6 to 11.1). The MDPP identified 15% of women with a previously unknown 10 year CVD QRISK2 of ≥10% and 56% with 10-year Qdiabetes risk of ≥10%.ConclusionsThe MDPP identified previously unknown CVD and T2D risk factors but does not appear to increase engagement with behaviour change beyond a standard BCPP amongst women attending breast screening. The results suggest a definitive effectiveness trial of the BCPP intervention is warranted, with acceptable uptake and retention, and a clear weight loss signal.Trial Registration ISRCTN91372184, https://doi.org/10.1186/ISRCTN91372184, registered 28 September 2014.