Abstract P3-11-01: Longitudinal Changes in Mammographic Features and Subsequent Risk of Breast Cancer in Pre-Menopausal Women: Studies Nested within the Age Trial

Abstract

Abstract Background: Mammographic percent density (PD) is one of the strongest known risk factors for breast cancer, with women with 75% or more density having approximately 4 times greater risk of developing breast cancer than those with little density (<5%). Most studies have been conducted in peri-and post-menopausal women with very few studies of density in younger pre-menopausal women. Mammographic features change throughout a woman's lifetime, with the amount of stromal and epithelial tissue decreasing with age, parity and the menopause. As some of the greatest changes in density occur during the menopause, it would be very informative to know whether PD measured at a younger age or the rate of change in PD could be better predictors of subsequent breast cancer risk. Methods: A nested case-control study of 350 cases and 450 controls was conducted within the intervention arm of the Age Trial of mammographic screening in young women, in which about 54,000 women wererandomised to receive yearly mammographic screening from ages 40 to 48. Women diagnosed with breast cancer were invited to participate in the study, and for each case, healthy controls were randomly selected matched to the cases on screening centre, age and date of mammogram. We are investigating how changes in PD over time in pre-menopausal women, measured on digitised films using a computer-assisted threshold method, relate to subsequent risk of breast cancer. Additionally, we are looking at associations of risk factor variables with baseline PD and changes in PD, investigated in longitudinal analyses in a sample of over 500 breast cancer-free women. Logistic regression models were used to estimate the effect of baseline mammographic density on subsequent breast cancer risk and multilevel linear models to assess the association between longitudinal changes in percent density and risk of breast cancer. Results: Over a 10 year period between ages 40 and 50, the mean reduction in percent density was 10.9% in our sample of breast cancer-free women. Change in percent density was greatest in the women's early forties, with a decrease of 1.9% per year, which reduced to about 0.2% in their late forties/early fifties. Baseline levels and rate of change of percent density were both associated with current and past anthropometric, reproductive and lifestyle factors. Change in percent density was associated with parity, with women who had three or more children experiencing a slower rate of change (P<0.01), and with body mass index (BMI), with extremely overweight women at baseline (>28 kg/m2) having a slower decline in PD than women of normal BMI (22-24 kg/m2). The analysis of the case-control data is currently in progress. Conclusion: We demonstrated that change in PD was associated with known breast cancer risk factors in pre-menopausal women. The results from the nested case-control study will further our understanding of the life-course trajectory of mammographic density and its role as a mediator of breast cancer risk. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-01.