Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, 710N. Fairbanks Court- Olson Pavilion, Suite 8-250A, Chicago, IL 60611, United States.
Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.
EBioMedicine. 2020 Aug;58:102914. doi: 10.1016/j.ebiom.2020.102914. Epub 2020 Jul 21.
We describe the genomic landscape of circulating tumour DNA (ctDNA) across pathological subtypes of metastatic breast cancer.
255 clinically annotated patients with ctDNA testing by Guardant360 were stratified into HR+, HER2+, and TNBC cohorts. Frequency and heterogeneity of alterations were reported. Paired ctDNA and tissue sequencing were compared for a subset of patients. The association of ctDNA and metastatic sites of disease on imaging was also assessed.
89% of patients had at least one ctDNA alteration detected. The most common single nucleotide variants (SNVs) for HR+ patients were PIK3CA, ESR1, and TP53. For HER2+, these were TP53, PIK3CA, and ERBB2 with ERBB2 as the most frequent copy number variant (CNV). For TNBC, the most common SNVs were TP53 and PIK3CA, and the most frequent CNVs were MYC, CCNE1, and PIK3CA. TNBC patients had a significantly higher mutant allele frequency (MAF) of the highest variant compared to HR+ or HER2+ patients (P<0.05). Overall, alterations in PIK3CA, ESR1, and ERBB2 were observed in 39.6%, 16.5%, and 21.6% of patients, respectively. Agreement between blood and tissue was 79-91%. MAF and number of alterations were significantly associated with number of metastatic sites on imaging (P<0.0001).
These data demonstrate the genetic heterogeneity of metastatic breast cancer in blood, the high prevalence of clinically actionable alterations, and the potential to utilise ctDNA as a surrogate for tumour burden on imaging.
Lynn Sage Cancer Research Foundation, OncoSET Precision Medicine Program, and REDCap support was funded by the National Institutes of Health UL1TR001422.
我们描述了转移性乳腺癌不同病理亚型的循环肿瘤 DNA（ctDNA）的基因组特征。
对 255 例接受 Guardant360 检测的具有临床注释的 ctDNA 患者进行分层，分为 HR+、HER2+和三阴性乳腺癌（TNBC）队列。报告了改变的频率和异质性。对部分患者进行了 ctDNA 和组织测序的比较。还评估了 ctDNA 与影像学上疾病转移部位的相关性。
89%的患者至少检测到一个 ctDNA 改变。HR+患者最常见的单核苷酸变异（SNVs）是 PIK3CA、ESR1 和 TP53。对于 HER2+，这些是 TP53、PIK3CA 和 ERBB2，其中 ERBB2 是最常见的拷贝数变异（CNV）。对于 TNBC，最常见的 SNVs 是 TP53 和 PIK3CA，最常见的 CNVs 是 MYC、CCNE1 和 PIK3CA。与 HR+或 HER2+患者相比，TNBC 患者的最高变异型的突变等位基因频率（MAF）明显更高（P<0.05）。总体而言，PIK3CA、ESR1 和 ERBB2 的改变分别在 39.6%、16.5%和 21.6%的患者中观察到。血液和组织之间的一致性为 79-91%。MAF 和改变数量与影像学上转移部位的数量显著相关（P<0.0001）。
这些数据表明，血液中转移性乳腺癌具有遗传异质性，临床上有治疗作用的改变发生率高，并且有可能利用 ctDNA 作为影像学肿瘤负荷的替代物。
林恩·塞奇癌症研究基金会、OncoSET 精准医学计划和 REDCap 的支持由美国国立卫生研究院 UL1TR001422 资助。
