Mandelblatt Jeanne, Schechter Clyde B, Lawrence William, Yi Bin, Cullen Jennifer
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
J Natl Cancer Inst Monogr. 2006(36):47-55. doi: 10.1093/jncimonographs/lgj008.
This stochastic simulation model was developed to estimate the impact of screening and treatment diffusion on U.S. breast cancer mortality between 1975 and 2000.
We use an event-driven continuous-time state transition model. Women who are destined to develop breast cancer may be screen detected, present with symptoms, or die of other causes before cancer is diagnosed. At presentation, the cancer has a stage assigned on the basis of mode of detection. Cancers are assumed to be estrogen receptor (ER) positive or negative. Data on screening and treatment diffusion are based on national datasets; other parameters are based on a synthesis of the evidence available in the literature.
The model is calibrated to predict incidence and stage distribution (in situ, local, regional, and distant). Other than screening or treatment, background events that affect mortality are not explicitly modeled but are captured in the deviation between model projections of mortality trends and actual trends. We assume that: 1) tumors progress more slowly in older age groups, 2) screen- and clinically detected disease have the same survival conditional on age and stage, 3) women do not die of breast cancer within the "lead time" period, 4) screening benefits are captured by shifts in stage at diagnosis, 4) tamoxifen benefits only ER-positive women, and 5) preclinical sojourn time and dwell times in each of the clinical stages are stochastically independent.
Dissemination of screening and therapeutic advances had a substantial impact on mortality trends. We estimate that, by the year 2000, diffusion of screening lowered mortality by 12.4% and treatment improvements and dissemination lowered mortality by 14.6%.
Models such as this one can be useful to translate clinical trial findings to general populations. This model can also be used inform policy debates about how to best achieve targeted reductions in breast cancer morbidity and mortality.
开发此随机模拟模型以估计1975年至2000年间筛查和治疗推广对美国乳腺癌死亡率的影响。
我们使用事件驱动的连续时间状态转换模型。注定会患乳腺癌的女性可能通过筛查被发现、出现症状或在癌症被诊断前死于其他原因。在确诊时,根据检测方式为癌症分配一个阶段。假设癌症为雌激素受体(ER)阳性或阴性。筛查和治疗推广的数据基于国家数据集;其他参数基于文献中现有证据的综合。
对模型进行校准以预测发病率和阶段分布(原位、局部、区域和远处)。除了筛查或治疗外,影响死亡率的背景事件未明确建模,但包含在死亡率趋势的模型预测与实际趋势之间的偏差中。我们假设:1)肿瘤在老年人群中进展较慢;2)经筛查和临床检测出的疾病在年龄和阶段相同的情况下具有相同的生存率;3)女性在“领先时间”内不会死于乳腺癌;4)筛查的益处通过诊断时阶段的变化体现;4)他莫昔芬仅对ER阳性女性有益;5)临床前停留时间和每个临床阶段的停留时间是随机独立的。
筛查和治疗进展的推广对死亡率趋势有重大影响。我们估计,到2000年,筛查的推广使死亡率降低了12.4%,治疗改善和推广使死亡率降低了14.6%。
这样的模型有助于将临床试验结果推广到一般人群。该模型还可用于为关于如何最好地实现有针对性地降低乳腺癌发病率和死亡率的政策辩论提供参考。