Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts.
Clin Cancer Res. 2021 Jun 15;27(12):3404-3413. doi: 10.1158/1078-0432.CCR-20-3444. Epub 2021 Jan 27.
Actionable mutations can guide genotype-directed matched therapy. We evaluated the utility of tissue-based and plasma-based genotyping for the identification of actionable mutations and selection of matched therapy in patients with metastatic breast cancer (MBC).
Patients with MBC who underwent tissue genotyping (institutional platform, 91-gene assay) or plasma-based cell-free DNA (cfDNA, Guardant360, 73-gene assay) between January 2016 and December 2017 were included. A chart review of records to identify subtype, demographics, treatment, outcomes, and tissue genotyping or cfDNA results was performed. The incidence of actionable mutations and the selection of matched therapy in tissue genotyping or cfDNA cohorts was determined. The impact of matched therapy status on overall survival (OS) in tissue genotyping or cfDNA subgroups was determined with Cox regression analysis.
Of 252 patients who underwent cfDNA testing, 232 (92%) had detectable mutations, 196 (78%) had actionable mutations, and 86 (34%) received matched therapy. Of 118 patients who underwent tissue genotyping, 90 (76%) had detectable mutations, 59 (50%) had actionable mutations, and 13 (11%) received matched therapy. For cfDNA patients with actionable mutations, matched versus nonmatched therapy was associated with better OS [HR 0.41, 95% confidence interval (CI): 0.23-0.73, = 0.002], and this remained significant in a multivariable analysis correcting for age, subtype, visceral metastases, and brain metastases (HR = 0.46, 95% CI: 0.26-0.83, = 0.010).
Plasma-based genotyping identified high rates of actionable mutations, which was associated with significant application of matched therapy and better OS in patients with MBC..
可操作的突变可以指导基于基因型的匹配治疗。我们评估了基于组织和血浆的基因分型在识别可操作的突变和选择转移性乳腺癌（MBC）患者的匹配治疗中的作用。
纳入 2016 年 1 月至 2017 年 12 月期间接受组织基因分型（机构平台，91 基因检测）或基于血浆的无细胞 DNA（cfDNA，Guardant360，73 基因检测）的 MBC 患者。对记录进行图表回顾，以确定亚型、人口统计学、治疗、结果以及组织基因分型或 cfDNA 结果。确定组织基因分型或 cfDNA 队列中可操作突变的发生率和匹配治疗的选择。使用 Cox 回归分析确定组织基因分型或 cfDNA 亚组中匹配治疗状态对总生存（OS）的影响。
在接受 cfDNA 检测的 252 例患者中，232 例（92%）有可检测到的突变，196 例（78%）有可操作的突变，86 例（34%）接受了匹配治疗。在接受组织基因分型的 118 例患者中，90 例（76%）有可检测到的突变，59 例（50%）有可操作的突变，13 例（11%）接受了匹配治疗。对于 cfDNA 患者有可操作的突变，匹配治疗与非匹配治疗相比，OS 更好[HR 0.41，95%置信区间（CI）：0.23-0.73， = 0.002]，在多变量分析中校正年龄、亚型、内脏转移和脑转移后仍然显著（HR = 0.46，95%CI：0.26-0.83， = 0.010）。
基于血浆的基因分型鉴定了高比例的可操作突变，这与 MBC 患者匹配治疗的广泛应用和更好的 OS 相关。
