Vidula Neelima, Niemierko Andrzej, Hesler Katherine, Ryan Lianne, Moy Beverly, Isakoff Steven, Ellisen Leif, Juric Dejan, Bardia Aditya
Massachusetts General Hospital Cancer Center, Boston, MA, 02114, USA.
NPJ Breast Cancer. 2023 Apr 19;9(1):29. doi: 10.1038/s41523-023-00528-z.
We compared cell-free DNA (cfDNA) results at MBC diagnosis in patients who developed brain metastases (BM) vs those without (non-BM) to understand genomic predictors of BM. Patients with cfDNA testing at MBC diagnosis (Guardant360®, 73 gene next generation sequencing) were identified. Clinical and genomic features of BM and non-BM were compared (Pearson's/Wilcoxon rank sum tests). Eighteen of 86 patients (21%) with cfDNA at MBC diagnosis developed BM. Comparing BM vs non-BM, a higher prevalence of BRCA2 (22% vs 4.4%, p = 0.01), APC (11% vs 0%, p = 0.005), CDKN2A (11% vs 1.5%, p = 0.05), and SMAD4 (11% vs 1.5%, p = 0.05) was observed. Seven of 18 BM had ≥1 of the following 4 mutations in baseline cfDNA: APC, BRCA2, CDKN2A or SMAD4 vs 5/68 non-BM (p = 0.001). Absence of this genomic pattern had a high negative predictive value (85%) and specificity (93%) in excluding BM development. Baseline genomic profile varies in MBC that develops BM.
我们比较了发生脑转移（BM）的转移性乳腺癌（MBC）患者与未发生脑转移（非BM）患者在MBC诊断时的游离DNA（cfDNA）结果，以了解BM的基因组预测指标。确定了在MBC诊断时进行cfDNA检测的患者（Guardant360®，73基因下一代测序）。比较了BM和非BM的临床和基因组特征（Pearson检验/ Wilcoxon秩和检验）。86例在MBC诊断时进行cfDNA检测的患者中有18例（21%）发生了BM。比较BM与非BM，观察到BRCA2（22%对4.4%，p = 0.01）、APC（11%对0%，p = 0.005）、CDKN2A（11%对1.5%，p = 0.05）和SMAD4（11%对1.5%，p = 0.05）的患病率更高。18例BM中有7例在基线cfDNA中具有以下4种突变中的≥1种：APC、BRCA2、CDKN2A或SMAD4，而非BM组为5/68（p = 0.001）。这种基因组模式的缺失在排除BM发生方面具有较高的阴性预测值（85%）和特异性（93%）。发生BM的MBC患者的基线基因组谱有所不同。
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