[Accepted Manuscript] Can dietary and physical activity modifications reduce breast density in postmenopausal women? The DAMA study, a randomized intervention trial in Italy

Few randomized trials have been carried out to evaluate the effect of lifestyle modifications on mammographic breast density (MBD). The randomized 2x2 factorial DAMA trial aimed to evaluate whether MBD can be reduced in post-menopausal women with high baseline MBD by a 24-months dietary and/or physical activity (PA) interventions. We randomized healthy post-menopausal women, attending the Florence (Italy) mammographic screening program, aged 50-69 years, non-smokers, with MBD>50% and no recent hormone therapy, to: a) a dietary intervention focused on plant-foods, with a low glycemic load, low in saturated fats and alcohol; b) a PA intervention combining daily moderate intensity activities and one weekly supervised session of more strenuous activity; c) both interventions; d) general recommendations. We evaluated changes in MBD based on VolparaTM estimates comparing baseline and follow-up digital mammograms by an intention-to-treat-analysis. MBD measures were available for 226 participants. An interaction emerged between treatments and thus we run analyses by arms. A decrease in volumetric percent density emerged for women in the dietary intervention (ratio 0.91; 95%CI 0.86-0.97; p=0.002) and in the PA intervention arm (0.93; 95%CI 0.87-0.98; p=0.01) in comparison with controls. No clear effect emerged in the double intervention arm. This intervention trial suggests that a 24-months dietary or PA intervention may reduce MBD in postmenopausal women. A modification of dietary habits or an increase in PA in postmenopausal women may reduce MBD. Further studies are needed to confirm these findings for planning breast cancer preventive strategies.