早期乳腺癌临床决策新工具开发验证
对于激素受体阳性、HER2阴性、淋巴结阴性的早期乳腺浸润癌术后女性，大约85%的患者复发风险较低，仅需内分泌治疗而不必化疗，其余患者复发风险较高，需要内分泌治疗联合化疗。患者年龄、临床特征、病理特征、合并症、多基因检测都有助于预测此类患者术后复发风险，决定是否需要化疗。不过，目前缺乏整合患者年龄、临床特征、病理特征、合并症、多基因检测的决策辅助工具。
2021年7月12日，美国临床肿瘤学会《临床肿瘤学杂志》在线发表乔治城大学、爱因斯坦医学院、斯坦福大学、凯萨医疗集团的研究报告，开发并验证了整合患者年龄、临床特征、病理特征、合并症±21基因检测的早期乳腺癌术后复发风险预测和临床决策新工具。
该研究利用现有癌症干预监测建模网络模拟模型，对10年远处复发风险、乳腺癌死亡率、其他原因死亡率、内分泌治疗±化疗相比寿命获益进行推算。根据年龄、肿瘤大小、分级、合并症评分±21基因复发评分的全部可能组合，模拟了1512例患者亚组的结局。模型数据来自临床试验、大型美国队列研究、登记数据库和医疗保险索赔数据。通过比较模拟结果与两个独立来源实际结果进行外部验证。该研究突出了治疗选择可能不确定时的结果。
结果，对于肿瘤≤2厘米、肿瘤分级中等、合并症轻度的65～69岁女性，内分泌治疗±化疗相比，10年远处复发风险绝对降低1.3%，寿命延长0.23年。
对于此类肿瘤患者，21基因复发评分16～20的概率为28%、21～25的概率为18%，≥26的概率为11%。
如果进行21基因检测，复发评分16～20，内分泌治疗±化疗相比，10年远处复发风险绝对降低1%，寿命延长0.20年，与未检测的结果相似。如果复发评分≥26，内分泌治疗±化疗相比，10年远处复发风险绝对值降低4.8%～5.5%。
该模型对于两个独立数据集的模拟结果与实际结果接近。
因此，该研究结果表明，对于激素受体阳性、HER2阴性、淋巴结阴性的早期乳腺浸润癌术后女性，该临床决策工具考虑了患者年龄、肿瘤大小、肿瘤分级、合并症±21基因复发评分检测结果，灵活、易于适应，包括新疗法，并且有助于早期乳腺癌多基因检测和术后辅助治疗方案的医患共同决策。
J Clin Oncol. 2021 Jul 12. Online ahead of print.
Development and Validation of a Simulation Model-Based Clinical Decision Tool: Identifying Patients Where 21-Gene Recurrence Score Testing May Change Decisions.
Jayasekera J, Sparano JA, O'Neill S, Chandler Y, Isaacs C, Kurian AW, Kushi L, Schechter CB, Mandelblatt J.
Georgetown University Medical Center, Washington, DC; Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; Albert Einstein College of Medicine, Bronx, NY; Stanford University School of Medicine, Stanford, CA; Kaiser Permanente Northern California, Oakland, CA.
PURPOSE: There is a need for industry-independent decision tools that integrate clinicopathologic features, comorbidities, and genomic information for women with node-negative, invasive, hormone receptor-positive, human epidermal growth factor receptor-2-negative (early-stage) breast cancer.
METHODS: We adapted an extant Cancer Intervention and Surveillance Modeling Network simulation model to estimate the 10-year risk of distant recurrence, breast cancer-specific mortality, other-cause mortality, and life-years gained with chemoendocrine versus endocrine therapy. We simulated outcomes for 1,512 unique patient subgroups based on all possible combinations of age, tumor size, grade, and comorbidity level; simulations were performed with and without 21-gene recurrence scores (RSs). Model inputs were derived from clinical trials, large US cohort studies, registry, and claims data. External validation was performed by comparing results to observed rates in two independent sources. We highlight results for one scenario where treatment choice may be uncertain.
RESULTS: Chemoendocrine versus endocrine therapy in a 65-69-year-old woman with a small (≤ 2 cm), intermediate-grade tumor, and mild comorbidities provides a 1.3% absolute reduction in 10-year distant recurrence risk, with 0.23 life-years gained. With these tumor features, a woman like this will have a 28% probability of having an RS 16-20, 18% RS 21-25, and 11% RS 26+. If testing is done, and her RS is 16-20, chemoendocrine therapy reduces 10-year distant recurrence risk to 1%, with 0.20 life-years gained, a similar result as without testing. The absolute benefits would increase to 4.8%-5.5% if the RS was 26+. The model closely reproduced observed rates in both independent data sets.
CONCLUSION: Our validated clinical decision tool is flexible, readily adaptable to include new therapies, and can support discussions about genomic testing and early breast cancer treatment.
KEY OBJECTIVE: The goal of this study was to develop and validate an independent clinical decision tool that integrates individual, clinical, and pathologic characteristics with 21-gene recurrence score assay information to guide adjuvant chemotherapy treatment decisions in women diagnosed with node-negative, invasive, hormone receptor-positive, human epidermal growth factor receptor-2-negative (early-stage) breast cancer.
KNOWLEDGE GENERATED: The novel simulation model-based web clinical decision tool (BTxChoice) provides the 10-year risk of distant recurrence and life-years gained with chemoendocrine versus endocrine therapy considering a woman's age, tumor size, tumor grade, and comorbidities with and without 21-gene recurrence score test results. The model closely reproduced observed rates in two independent data sets.
RELEVANCE: The BTxChoice tool provides useful information to facilitate shared decision making about the use of genomic testing and adjuvant chemotherapy in early-stage breast cancer.
PMID: 34251881
DOI: 10.1200/JCO.21.00651