Altarum Institute, 3520 Green Court, Suite 300, Ann Arbor, MI 48105, USA.
Expert Rev Pharmacoecon Outcomes Res. 2011 Jun;11(3):325-41. doi: 10.1586/erp.11.25.
To evaluate the clinical outcomes and cost-effectiveness of human epidermal growth factor receptor 2 (HER2) testing strategies to guide adjuvant trastuzumab (AT) therapy in women with HER2-positive breast cancer.
A literature review produced 72 studies comparing HER2 test methods, and we computed concordance (assuming fluorescence in situ hybridization [FISH] as a reference assay) to assess performance relative to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. An economic analysis provided cost-effectiveness of alternative strategies, including a Monte Carlo simulation to vary key assumptions such as test price and performance.
Of 46 studies comparing immunohistochemistry (IHC) and FISH, only seven met the ASCO/CAP guideline of 95% or better concordance. A total of 14 out of 21 studies comparing chromogenic in situ hybridization and three out of five studies comparing silver-enhanced in situ hybridization met the guideline. Confirmation of IHC 2+ and 3+ and primary FISH strategies are likely to reduce costs and improve quality of life relative to confirmation of IHC 2+ only. Initial testing with a gene amplification-based assay is probably a cost-effective alternative to confirmation of IHC 2+ and 3+. The results are not sensitive to varying test price but are sensitive to test accuracy below 98%.
Using a primary gene amplification-based assay to guide AT therapy for HER2-positive breast cancer probably results in lower US medical costs, increased life-years and increased quality of life compared with confirmation of IHC 2+ with a gene amplification-based assay. We recommend the ASCO/CAP guidelines reflect 98% or greater concordance relative to a reference assay. Additional research regarding therapy response is required to further differentiate between gene amplification-based assays.
评估人表皮生长因子受体 2（HER2）检测策略指导曲妥珠单抗（AT）辅助治疗 HER2 阳性乳腺癌的临床结局和成本效益。
文献综述产生了 72 项比较 HER2 检测方法的研究，我们计算了一致性（假设荧光原位杂交 [FISH] 作为参考检测方法），以评估相对于美国临床肿瘤学会/美国病理学家协会（ASCO/CAP）指南的性能。经济分析提供了替代策略的成本效益，包括使用蒙特卡罗模拟来改变关键假设，例如测试价格和性能。
在比较免疫组织化学（IHC）和 FISH 的 46 项研究中，只有 7 项符合 ASCO/CAP 指南的 95%或更高一致性。在比较显色原位杂交的 21 项研究中，共有 14 项符合该指南，在比较银增强原位杂交的 5 项研究中，有 3 项符合该指南。与仅确认 IHC 2+和 3+相比，确认 IHC 2+和 FISH 以及初始 FISH 策略可能会降低成本并提高生活质量。与仅确认 IHC 2+相比，基于基因扩增的初始检测可能是一种具有成本效益的替代方案。结果对测试价格的变化不敏感，但对测试准确性低于 98%的情况很敏感。
与使用基于基因扩增的检测方法确认 IHC 2+相比，使用基于基因扩增的初始检测方法指导曲妥珠单抗治疗 HER2 阳性乳腺癌可能会降低美国医疗成本，增加寿命和提高生活质量。我们建议 ASCO/CAP 指南反映相对于参考检测方法的 98%或更高的一致性。需要进一步研究治疗反应，以进一步区分基于基因扩增的检测方法。
