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.

中文翻译：

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乳腺癌淋巴结转移的随机效应模型：量化协变量的作用并使用连续生长模型进行筛查

我们最近描述了一个乳腺癌肿瘤大小和受影响淋巴结数量的联合模型，该模型取决于筛查历史、乳房 X 线摄影密度和检测模式，可用于推断生长率、症状检测时间、筛查敏感性和淋巴结扩散率。淋巴结扩散模型可以独立于肿瘤体积和受影响淋巴结数量的测量值来估计，从而得出与联合模型相同的推论。在这里，我们扩展我们的模型以包括协变量效应。我们还得出了理论结果，以研究筛查在诊断时对淋巴结转移的作用。我们分析了激素替代疗法 (HRT) 与乳腺癌淋巴结扩散之间的关系，使用来自专为研究 HRT 对乳腺癌的影响而设计的病例对照研究的数据。使用我们的方法，我们估计在诊断时使用 HRT 的女性的淋巴结扩散率比不使用 HRT 的女性低 36%（95% 置信区间 [CI] =(8%,58%)）。这可以与 HRT 对肿瘤生长速率的影响形成对比，在此估计 HRT 使用者慢 15% (95% CI = (-34%,+7%))。对于筛查发现的癌症，我们说明了提前期与淋巴结扩散的关系；并使用有症状的癌症，我们说明了假阴性筛查在淋巴结扩散方面的潜在后果。这可以与 HRT 对肿瘤生长速率的影响形成对比，在此估计 HRT 使用者慢 15% (95% CI = (-34%,+7%))。对于筛查发现的癌症，我们说明了提前期与淋巴结扩散的关系；并使用有症状的癌症，我们说明了假阴性筛查在淋巴结扩散方面的潜在后果。这可以与 HRT 对肿瘤生长速率的影响形成对比，在此估计 HRT 使用者慢 15% (95% CI = (-34%,+7%))。对于筛查发现的癌症，我们说明了提前期与淋巴结扩散的关系；并使用有症状的癌症，我们说明了假阴性筛查在淋巴结扩散方面的潜在后果。