Lynge Elsebeth, Vejborg Ilse, Andersen Zorana, von Euler-Chelpin My, Napolitano George
Nykøbing Falster Hospital, University of Copenhagen, Ejegodvej 63, DK-4800 Nykøbing Falster, Denmark.
Radiology Clinic, Copenhagen University Hospital, Rigshospitalet, DK-2100 København Ø, Denmark.
J Clin Med. 2019 Nov 19;8(11):2021. doi: 10.3390/jcm8112021.
Attention in the 2000s on the importance of mammographic density led us to study screening sensitivity, breast cancer incidence, and associations with risk factors by mammographic density in Danish breast cancer screening programs. Here, we summarise our approaches and findings.
Dichotomized density codes: fatty, equal to BI-RADS density code 1 and part of 2, and other mixed/dense data from the 1990s-were available from two counties, and BI-RADS density codes from one region were available from 2012/13. Density data were linked with data on vital status, incident breast cancer, and potential risk factors. We calculated screening sensitivity by combining data on screen-detected and interval cancers. We used cohorts to study high density as a predictor of breast cancer risk; cross-sectional data to study the association between life style factors and density, adjusting for age and body mass index (BMI); and time trends to study the prevalence of high density across birth cohorts.
Sensitivity decreased with increasing density from 78% in women with BI-RADS 1 to 47% in those with BI-RADS 4. For women with mixed/dense compared with those with fatty breasts, the rate ratio of incident breast cancer was 2.45 (95% CI 2.14-2.81). The percentage of women with mixed/dense breasts decreased with age, but at a higher rate the later the women were born. Among users of postmenopausal hormone therapy, the percentage of women with mixed/dense breasts was higher than in non-users, but the patterns across birth cohorts were similar. The occurrence of mixed/dense breast at screening age decreased by a z-score unit of BMI at age 13-odds ratio (OR) 0.56 (95% CI 0.53-0.58)-and so did breast cancer risk and hazard ratio (HR) 0.92 (95% CI 0.84-1.00), but it changed to HR 1.01 (95% CI 0.93-1.11) when controlled for density. Age and BMI adjusted associations between life style factors and density were largely close to unity; physical activity OR 1.06 (95% CI 0.93-1.21); alcohol consumption OR 1.01 (95% CI 0.81-1.27); air pollution OR 0.96 (95% 0.93-1.01) per 20 μg/m; and traffic noise OR 0.94 (95% CI 0.86-1.03) per 10 dB. Weak negative associations were seen for diabetes OR 0.61 (95% CI 0.40-0.92) and cigarette smoking OR 0.86 (95% CI 0.75-0.99), and a positive association was found with hormone therapy OR 1.24 (95% 1.14-1.35).
Our data indicate that breast tissue in middle-aged women is highly dependent on childhood body constitution while adult life-style plays a modest role, underlying the need for a long-term perspective in primary prevention of breast cancer.
21世纪对乳腺X线密度重要性的关注促使我们在丹麦乳腺癌筛查项目中，研究筛查敏感性、乳腺癌发病率以及乳腺X线密度与风险因素之间的关联。在此，我们总结我们的方法和研究结果。
二分密度编码：来自两个县的脂肪型（等同于乳腺影像报告和数据系统（BI-RADS）密度编码1以及部分编码2），以及20世纪90年代的其他混合/致密数据，还有来自一个地区的2012/13年的BI-RADS密度编码。密度数据与生命状态、新发乳腺癌以及潜在风险因素的数据相链接。我们通过合并筛查发现的癌症和间期癌的数据来计算筛查敏感性。我们使用队列研究高密度作为乳腺癌风险的预测指标；使用横断面数据研究生活方式因素与密度之间的关联，并对年龄和体重指数（BMI）进行校正；使用时间趋势研究不同出生队列中高密度的患病率。
敏感性随着密度增加而降低，从BI-RADS 1的女性中的78%降至BI-RADS 4的女性中的47%。与脂肪型乳房的女性相比，混合/致密型乳房的女性新发乳腺癌的发病率比为2.45（95%可信区间2.14 - 2.81）。混合/致密型乳房的女性比例随年龄下降，但女性出生越晚下降速度越快。在绝经后激素治疗使用者中，混合/致密型乳房的女性比例高于非使用者，但不同出生队列的模式相似。筛查年龄时混合/致密型乳房的出现率随13岁时BMI的z评分单位下降——比值比（OR）为0.56（95%可信区间0.53 - 0.58）——乳腺癌风险和风险比（HR）也如此，为0.92（95%可信区间0.84 - 1.00），但在控制密度后变为HR 1.01（95%可信区间0.93 - 1.11）。年龄和BMI校正后的生活方式因素与密度之间的关联大多接近1；身体活动OR为1.06（95%可信区间0.93 - 1.21）；饮酒OR为1.01（95%可信区间0.81 - 1.27）；空气污染每增加20μg/m³，OR为0.96（95% 0.93 - 1.01）；交通噪音每增加10dB，OR为0.94（95%可信区间0.86 - 1.03）。糖尿病OR为0.61（95%可信区间0.40 - 0.92）和吸烟OR为0.86（95%可信区间0.75 - 0.99）呈现弱负相关，激素治疗OR为1.24（95% 1.14 - 1.35）呈现正相关。
我们的数据表明中年女性的乳腺组织高度依赖儿童期身体体质，而成年生活方式起的作用较小，这凸显了在乳腺癌一级预防中需要有长期视角。
