Illipse Maya, Gasparini Alessandro, Christoffersen Benjamin, Hall Per, Czene Kamila, Humphreys Keith
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden.
Department of Oncology, Södersjukhuset, 11883 Stockholm, Sweden.
Am J Epidemiol. 2025 Apr 8;194(4):1065-1071. doi: 10.1093/aje/kwae196.
Conflicting results have appeared in the literature on whether the amount of nondense, adipose tissue in the breast is a risk factor or a protective factor for breast cancer (BC), and biological hypotheses supporting both have been proposed. We suggest here that limitations in study design and statistical methodology could potentially explain the inconsistent results. Specifically, we exploit recent advances in methodology and software developed for the joint analysis of multiple longitudinal outcomes and time-to-event data to jointly analyze dense and nondense tissue trajectories and the risk of BC in a large Swedish screening cohort. We also perform extensive sensitivity analyses by mimicking analyses/designs of previously published studies-for example, ignoring available longitudinal data. Overall, we do not find strong evidence supporting an association between nondense tissue and the risk of incident BC. We hypothesize that (1) previous studies have not been able to isolate the effect of nondense tissue from dense tissue or adipose tissue elsewhere in the body, that (2) estimates of the effect of nondense tissue on risk are strongly sensitive to modeling assumptions, or that (3) the effect size of nondense tissue on BC risk is likely to be small/not clinically relevant.
关于乳腺中低密度脂肪组织的量是乳腺癌（BC）的危险因素还是保护因素，文献中出现了相互矛盾的结果，并且已经提出了支持这两种观点的生物学假说。我们在此表明，研究设计和统计方法的局限性可能潜在地解释了这些不一致的结果。具体而言，我们利用为多个纵向结局和事件发生时间数据的联合分析而开发的方法和软件的最新进展，对瑞典一个大型筛查队列中的致密和非致密组织轨迹以及BC风险进行联合分析。我们还通过模仿先前发表研究的分析/设计（例如，忽略可用的纵向数据）来进行广泛的敏感性分析。总体而言，我们没有发现有力证据支持非致密组织与新发BC风险之间存在关联。我们假设：（1）先前的研究未能将非致密组织的影响与致密组织或身体其他部位的脂肪组织的影响区分开来；（2）非致密组织对风险影响的估计对建模假设高度敏感；或者（3）非致密组织对BC风险的效应大小可能很小/在临床上不相关。
