Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Department of Public Health, Erasmus MC, Rotterdam, The Netherlands.
Med Decis Making. 2021 Apr;41(3):354-365. doi: 10.1177/0272989X21991173. Epub 2021 Mar 3.
Genomic tests may improve upon clinical risk estimation with traditional prognostic factors. We aimed to explore how evidence on the prognostic strength of a genomic signature (clinical validity) can contribute to individualized decision making on starting chemotherapy for women with breast cancer (clinical utility).
The MINDACT trial was a randomized trial that enrolled 6693 women with early-stage breast cancer. A 70-gene signature (Mammaprint) was used to estimate genomic risk, and clinical risk was estimated by a dichotomized version of the Adjuvant!Online risk calculator. Women with discordant risk results were randomized to the use of chemotherapy. We simulated the full risk distribution of these women and estimated individual benefit, assuming a constant relative effect of chemotherapy.
The trial showed a prognostic effect of the genomic signature (adjusted hazard ratio 2.4). A decision-analytic modeling approach identified far fewer women as candidates for genetic testing (4% rather than 50%) and fewer benefiting from chemotherapy (3% rather than 27%) as compared with the MINDACT trial report. The selection of women benefitting from genetic testing and chemotherapy depended strongly on the required benefit from treatment and the assumed therapeutic effect of chemotherapy.
A high-quality pragmatic trial was insufficient to directly inform clinical practice on the utility of a genomic test for individual women. The indication for genomic testing may be far more limited than suggested by the MINDACT trial.
基因组测试可以通过传统的预后因素提高临床风险评估。我们旨在探讨基因组特征（临床有效性）的预后强度证据如何有助于对患有乳腺癌的女性开始化疗的个体化决策（临床实用性）。
MINDACT 试验是一项随机试验，共纳入了 6693 例早期乳腺癌患者。使用 70 个基因的特征（Mammaprint）来估计基因组风险，临床风险通过 Adjuvant!Online 风险计算器的二分类版本来估计。风险结果不一致的女性被随机分配使用化疗。我们模拟了这些女性的完整风险分布，并假设化疗的相对效果恒定，从而估计了个体的获益。
该试验显示了基因组特征的预后效果（调整后的危险比为 2.4）。决策分析模型方法确定了更少的女性适合进行基因检测（4%而不是 50%），更少的女性从化疗中获益（3%而不是 27%），与 MINDACT 试验报告相比。从基因检测和化疗中获益的女性的选择强烈取决于治疗的预期获益和假设的化疗治疗效果。
一项高质量的实用试验不足以直接为个体女性提供基因组测试的实用性提供临床实践依据。基因检测的指征可能比 MINDACT 试验所表明的要局限得多。
