Dowty James G, Byrnes Graham B, Gertig Dorota M
Melbourne School of Population and Global Health, University of Melbourne, Level 3/207 Bouverie St., Carlton 3053, Australia
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon cedex 08, France.
Math Med Biol. 2014 Dec;31(4):353-64. doi: 10.1093/imammb/dqt014. Epub 2013 Jul 19.
Ductal carcinoma in situ (DCIS) lesions are non-invasive tumours of the breast that are thought to precede most invasive breast cancers (IBCs). As individual DCIS lesions are initiated, grow and invade (i.e. become IBC), the size distribution of the DCIS lesions present in a given human population will evolve. We derive a differential equation governing this evolution and show, for given assumptions about growth and invasion, that there is a unique distribution which does not vary with time. Further, we show that any initial distribution converges to this stationary distribution exponentially quickly. Therefore, it is reasonable to assume that the stationary distribution governs the size of DCIS lesions in human populations which are relatively stable with respect to the determinants of breast cancer. Based on this assumption and the size data of 110 DCIS lesions detected in a mammographic screening programme between 1993 and 2000, we produce maximum likelihood estimates for certain growth and invasion parameters. Assuming that DCIS size is proportional to a positive power p of the time since tumour initiation, we estimate p to be 0.50 with a 95% confidence interval of (0.35, 0.71). Therefore, we estimate that DCIS lesions follow a square-root growth law and hence that they grow rapidly when small and relatively slowly when large. Our approach and results should be useful for other mathematical studies of cancer, especially those investigating biological mechanisms of invasion.
导管原位癌(DCIS)病变是乳腺的非侵袭性肿瘤,被认为是大多数浸润性乳腺癌(IBC)的前驱病变。随着单个DCIS病变的发生、生长和侵袭(即变为IBC),特定人群中存在的DCIS病变的大小分布将会演变。我们推导了一个描述这种演变的微分方程,并表明,在关于生长和侵袭的给定假设下,存在一种不随时间变化的唯一分布。此外,我们表明任何初始分布都以指数速度快速收敛到这种平稳分布。因此,有理由假设平稳分布决定了在乳腺癌决定因素方面相对稳定的人群中DCIS病变的大小。基于这一假设以及在1993年至2000年的乳腺钼靶筛查项目中检测到的110个DCIS病变的大小数据,我们对某些生长和侵袭参数进行了最大似然估计。假设DCIS大小与肿瘤发生后的时间的正幂p成正比,我们估计p为0.50,95%置信区间为(0.35, 0.71)。因此,我们估计DCIS病变遵循平方根生长规律,从而它们在较小时生长迅速,在较大时生长相对缓慢。我们的方法和结果应该对癌症的其他数学研究有用,特别是那些研究侵袭生物学机制的研究。