Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Biometrics. 2022 Mar;78(1):376-387. doi: 10.1111/biom.13430. Epub 2021 Feb 7.
We recently described a joint model of breast cancer tumor size and number of affected lymph nodes, which conditions on screening history, mammographic density, and mode of detection, and can be used to infer growth rates, time to symptomatic detection, screening sensitivity, and rates of lymph node spread. The model of lymph node spread can be estimated in isolation from measurements of tumor volume and number of affected lymph nodes, giving inference identical to the joint model. Here, we extend our model to include covariate effects. We also derive theoretical results in order to study the role of screening on lymph node metastases at diagnosis. We analyze the association between hormone replacement therapy (HRT) and breast cancer lymph node spread, using data from a case-control study designed specifically to study the effects of HRT on breast cancer. Using our method, we estimate that women using HRT at time of diagnosis have a 36% lower rate of lymph node spread than nonusers (95% confidence interval [CI] =(8%,58%)). This can be contrasted with the effect of HRT on the tumor growth rate, estimated here to be 15% slower in HRT users (95% CI = (-34%,+7%)). For screen-detected cancers, we illustrate how lead time can relate to lymph node spread; and using symptomatic cancers, we illustrate the potential consequences of false negative screens in terms of lymph node spread.
我们最近描述了一个联合模型，用于预测乳腺癌肿瘤大小和受累淋巴结数量，该模型考虑了筛查史、乳腺密度和检测方式等因素，可以用于推断生长速度、症状出现前的时间、筛查敏感性和淋巴结转移率。该模型可以在不考虑肿瘤体积和受累淋巴结数量的情况下单独估计淋巴结转移情况，其推断结果与联合模型相同。在这里，我们将模型扩展到包括协变量效应。我们还推导出了一些理论结果，以研究筛查对诊断时淋巴结转移的作用。我们使用一项专门用于研究激素替代疗法 (HRT) 对乳腺癌影响的病例对照研究的数据，分析了激素替代疗法 (HRT) 与乳腺癌淋巴结转移之间的关系。使用我们的方法，我们估计在诊断时使用 HRT 的女性淋巴结转移率比未使用者低 36%（95%置信区间 [CI] =（8%，58%））。这与 HRT 对肿瘤生长速度的影响形成对比，在这里估计 HRT 使用者的肿瘤生长速度慢 15%（95% CI =（-34%，+7%））。对于筛查发现的癌症，我们说明了如何将领先时间与淋巴结转移联系起来；并使用症状性癌症，说明了假阴性筛查在淋巴结转移方面的潜在后果。
