Health Equity and Decision Sciences Laboratory, National Institute on Minority Health and Health Disparities, Division of Intramural Research, National Institutes of Health, Bethesda, MD, USA.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
BMC Cancer. 2024 Aug 8;24(1):975. doi: 10.1186/s12885-024-12719-3.
A recent trial showed that postmenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor-2 (HER2)-negative, lymph node-positive (1-3 nodes) breast cancer with a 21-gene recurrence score of ≤ 25 could safely omit chemotherapy. However, there are limited data on population-level long-term outcomes associated with omitting chemotherapy among diverse women seen in real-world practice.
We adapted an established, validated simulation model to generate the joint distributions of population-level characteristics of women diagnosed with early-stage breast cancer in the U.S. Input parameters were derived from cancer registry, meta-analyses, and clinical trial data. The effects of omitting chemotherapy on 10-year distant recurrence-free survival, life-years, and quality adjusted life-years (QALYs) were modeled for premenopausal and postmenopausal women. QALYs were discounted at 3%. Results were evaluated for subgroups stratified by race and ethnicity. Sensitivity analyses included testing results across a range of inputs. The model was validated using the published RxPONDER trial data.
In premenopausal women, the 10-year distant recurrence-free survival rates were 85.3% with chemo-endocrine and 80.1% with endocrine therapy. The estimated life-years and QALYs gained with chemotherapy in premenopausal women were 2.1 and 0.6, respectively. There was no chemotherapy benefit in postmenopausal women. There was no variation in the absolute benefit of chemotherapy across racial or ethnic subgroups. However, there were differences in distant recurrence-free survival rates, life-years, and QALYs across groups. Sensitivity analysis showed similar results. The model closely replicated the RxPONDER trial.
Modeled population-level outcomes show a small chemotherapy benefit in premenopausal women, but no benefit among postmenopausal women. Simulation modeling provides a useful tool to extend trial data and evaluate population-level outcomes.
最近的一项试验表明，激素受体阳性、人表皮生长因子受体 2（HER2）阴性、淋巴结阳性（1-3 个淋巴结）的绝经后妇女，21 基因复发评分≤25 ，可安全省略化疗。然而，在真实世界实践中，对于不同女性群体中省略化疗的人群水平长期结局，数据有限。
我们采用了一种已建立的、经过验证的模拟模型，生成美国早期乳腺癌患者的人群水平特征的联合分布。输入参数来自癌症登记处、荟萃分析和临床试验数据。对绝经前和绝经后妇女省略化疗对 10 年远处无复发生存率、寿命年和质量调整寿命年（QALY）的影响进行了建模。QALY 贴现率为 3%。根据种族和民族进行亚组分层，评估结果。敏感性分析包括在一系列输入中测试结果。该模型使用已发表的 RxPONDER 试验数据进行了验证。
在绝经前妇女中，化疗内分泌治疗的 10 年远处无复发生存率为 85.3%，内分泌治疗为 80.1%。化疗可使绝经前妇女获得的寿命年和 QALY 分别增加 2.1 年和 0.6 年。绝经后妇女没有化疗获益。不同种族或民族亚组的化疗绝对获益没有差异。然而，不同组别的远处无复发生存率、寿命年和 QALY 存在差异。敏感性分析显示出类似的结果。该模型很好地复制了 RxPONDER 试验。
模型化的人群水平结果显示，化疗对绝经前妇女有较小的获益，但对绝经后妇女没有获益。模拟建模为扩展试验数据和评估人群水平结局提供了有用的工具。
