尽管乳腺密度是乳腺癌的已知风险因素，但乳腺密度的纵向变化尚未得到广泛研究，以确定该因素是否与乳腺癌风险相关。本研究旨在前瞻性评估每个乳房乳腺密度变化与随后乳腺癌风险之间的关联。该研究采用嵌套病例-对照队列研究方法，从10481名入组时没有癌症的女性中抽样，观察时间为2008年11月3日至2020年10月31日，每1至2年进行例行筛查乳腺X线摄影，提供乳腺密度测量。该研究在圣路易斯地区为多样化人群提供乳腺癌筛查。共识别出289例经组织病理学证实的乳腺癌病例，根据入组时的年龄和入组年份，每名病例抽取约2名对照，共得658名对照，分析了8710份头脚位乳腺X线摄影。暴露因素包括筛查乳腺X线摄影中的体积百分比密度、乳腺密度体积随时间的变化以及经乳腺活检证实的癌症。通过问卷调查收集了乳腺癌风险因素。根据每个女性的病例和对照状态，纵向观察每个女性乳腺体积密度的变化情况。947名参与者入组时的平均（标准差）年龄为56.67（8.71）岁；其中141人是黑人（14.9％），763人是白人（80.6％），20人是其他种族或族裔（2.1％），23人未报告此信息（2.4％）。最后一次乳腺X线摄影到随后乳腺癌诊断日期的平均（标准差）间隔为2.0（1.5）年（第10百分位数为1.0年，第90百分位数为3.9年）。病例和对照组的乳腺密度随时间均有所下降。然而，患有乳腺癌的乳房乳腺密度下降速率的下降幅度明显较慢，与对照组相比（估计值=0.027，95％CI为0.001-0.053，P=0.04）。本研究发现，乳腺密度的变化速率与随后乳腺癌的风险相关。将纵向变化纳入现有模型中，可优化风险分层和指导更个性化的风险管理。

Although breast density is an established risk factor for breast cancer, longitudinal changes in breast density have not been extensively studied to determine whether this factor is associated with breast cancer risk.To prospectively evaluate the association between change in mammographic density in each breast over time and risk of subsequent breast cancer.This nested case-control cohort study was sampled from the Joanne Knight Breast Health Cohort of 10 481 women free from cancer at entry and observed from November 3, 2008, to October 31, 2020, with routine screening mammograms every 1 to 2 years, providing a measure of breast density. Breast cancer screening was provided for a diverse population of women in the St Louis region. A total of 289 case patients with pathology-confirmed breast cancer were identified, and approximately 2 control participants were sampled for each case according to age at entry and year of enrollment, yielding 658 controls with a total number of 8710 craniocaudal-view mammograms for analysis.Exposures included screening mammograms with volumetric percentage of density, change in volumetric breast density over time, and breast biopsy pathology-confirmed cancer. Breast cancer risk factors were collected via questionnaire at enrollment.Longitudinal changes over time in each woman's volumetric breast density by case and control status.The mean (SD) age of the 947 participants was 56.67 (8.71) years at entry; 141 were Black (14.9%), 763 were White (80.6%), 20 were of other race or ethnicity (2.1%), and 23 did not report this information (2.4%). The mean (SD) interval was 2.0 (1.5) years from last mammogram to date of subsequent breast cancer diagnosis (10th percentile, 1.0 year; 90th percentile, 3.9 years). Breast density decreased over time in both cases and controls. However, there was a significantly slower decrease in rate of decline in density in the breast that developed breast cancer compared with the decline in controls (estimate = 0.027; 95% CI, 0.001-0.053; P = .04).This study found that the rate of change in breast density was associated with the risk of subsequent breast cancer. Incorporation of longitudinal changes into existing models could optimize risk stratification and guide more personalized risk management.