Differences in Mammographic Density Decline over Time in Breast Cancer Cases and Women at High Risk for Breast Cancer

Introduction: High absolute breast density and increased breast density over time are strongly associated with breast cancer risk, and breast density generally decreases with increasing age. We examined mammographic density data from members of the Women At Risk High-Risk Registry at Columbia University Medical Center (WAR), a cohort defined as at high risk for breast cancer due to family history of breast cancer, history of lobular carcinoma in situ, and/or benign breast disease, to determine changes in their breast density over time. Methods: Within the WAR cohort of 1598 women, we conducted a nested case-control study of 66 incident cases of invasive breast cancer and 70 women without cancer, matched on age and time between first and second mammogram. For each participant, we collected two mammograms (for the cases, both mammograms occurred before cancer diagnosis), to examine differences in absolute density, percent density, and change in density between cases and controls. The average time between first and second mammogram was 4.6 years for both cases and controls, with a range of between 1 and 15 years. Results: Using linear regression with change in percent density as the outcome, and time between first and second mammogram as the independent variable, we found that among women without breast cancer, density decreased as time between first and second mammogram increased (β = −2.15, p = 0.005). In contrast, there was no overall change in density among the cases associated with time between first and second mammogram (β = 0.69, p = 0.39). In an ANCOVA comparing the slopes of the regression lines, the slopes were significantly different for cases versus controls (p = 0.009). Conclusion: In a cohort of women at high risk for breast cancer, breast density does not decrease as time between mammograms increases, for women who go on to develop breast cancer. For women who do not develop breast cancer, breast density decreases significantly over time.