Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk

Background: Whether a change over time in clinically measured mammographic breast density influences breast cancer risk is unknown. Methods: From January 1993 to December 2003, data that included American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) breast density categories (1-4 in order of increasing density) were collected prospectively on 301 955 women aged 30 and older who were not using postmenopausal hormone replacement therapy and underwent at least two screening mammography examinations; 2639 of the women were diagnosed with breast cancer within 1 year of the last examination. Women's first and last BI-RADS breast density (average 3.2 years apart) and logistic regression were used to model the odds of having invasive breast cancer or ductal carcinoma in situ diagnosed within 12 months of the last examination by change in BI-RADS category. Rates of breast cancer adjusted for age, mammography registry, and time between screening examinations were estimated from this model. All statistical tests were two-sided. Results: The rate (breast cancers per 1000 women) of breast cancer was higher if BI-RADS breast density category increased from 1 to 2 (5.6, 95% confidence interval [CI] = 4.7 to 6.9) or 1 to 3 (9.9, 95% CI = 6.4 to 15.5) compared to when it remained at BI-RADS density of 1 (3.0, 95% CI = 2.3 to 3.9; P <.001 for trend). Similar and statistically significant trends between increased or decreased density and increased or decreased risk of breast cancer, respectively, were observed for women whose breast density category was initially 2 or 3 and changed categories. BI-RADS density of 4 on the first examination was associated with a high rate of breast cancer (range 9.1-13.4) that remained high even if breast density decreased. Conclusion: An increase in BI-RADS breast density category within 3 years may be associated with an increase in breast cancer risk and a decrease in density category with a decrease in risk compared to breast cancer risk in women in whom breast density category remains unchanged. Two longitudinal measures of BI-RADS breast density may better predict a woman's risk of breast cancer than a single measure.