Takeshita Takashi, Yamamoto Yutaka, Yamamoto-Ibusuki Mutsuko, Tomiguchi Mai, Sueta Aiko, Murakami Keiichi, Omoto Yoko, Iwase Hirotaka
Department of Breast and Endocrine Surgery, Graduate School of Medical Science, Kumamoto University, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Department of Molecular-Targeting Therapy for Breast Cancer, Kumamoto University Hospital, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Transl Oncol. 2017 Oct;10(5):766-771. doi: 10.1016/j.tranon.2017.07.004. Epub 2017 Aug 1.
ESR1 mutation in circulating cell-free DNA (cfDNA) is emerging as a noninvasive biomarker of acquired resistance to endocrine therapy, but there is a paucity of data comparing the status of ESR1 gene in cfDNA with that in its corresponding tumor tissue. The objective of this study is to validate the degree of concordance of ESR1 mutations between plasma and tumor tissue.
ESR1 ligand-binding domain mutations Y537S, Y537N, Y537C, and D538G were analyzed using droplet digital PCR in 35 patients with metastatic breast cancer (MBC) (35 tumor tissue samples and 67 plasma samples).
Of the 35 paired samples, 26 (74.3%) were concordant: one patient had detectable ESR1 mutations both plasma (ESR1 Y537S/Y537N) and tumor tissue (ESR1 Y537S/Y537C), and 25 had WT ESR1 alleles in both. Nine (25.7%) had discordance between the plasma and tissue results: five had mutations detected only in their tumor tissue (two Y537S, one Y537C, one D538G, and one Y537S/Y537N/D538G), and four had mutations detected only in their plasma (one Y537S, one Y537N, and two Y537S/Y537N/D538G). Furthermore, longitudinal plasma samples from 19 patients were used to assess changes in the presence of ESR1 mutations during treatment. Eleven patients had cfDNA ESR1 mutations over the course of treatment. A total of eight of 11 patients with MBC with cfDNA ESR1 mutations (72.7%) had the polyclonal mutations.
We have shown the independent distribution of ESR1 mutations between plasma and tumor tissue in 35 patients with MBC.
循环游离DNA（cfDNA）中的ESR1突变正逐渐成为内分泌治疗获得性耐药的一种非侵入性生物标志物，但将cfDNA中ESR1基因的状态与其相应肿瘤组织中的状态进行比较的数据较少。本研究的目的是验证血浆与肿瘤组织中ESR1突变的一致程度。
采用液滴数字PCR分析35例转移性乳腺癌（MBC）患者（35份肿瘤组织样本和67份血浆样本）的ESR1配体结合域突变Y537S、Y537N、Y537C和D538G。
在35对样本中，26对（74.3%）结果一致：1例患者血浆（ESR1 Y537S/Y537N）和肿瘤组织（ESR1 Y537S/Y537C）中均检测到ESR1突变，25例患者血浆和肿瘤组织中ESR1等位基因均为野生型。9对（25.7%）血浆和组织结果不一致：5例仅在肿瘤组织中检测到突变（2例Y537S、1例Y537C、1例D538G和1例Y537S/Y537N/D538G），4例仅在血浆中检测到突变（1例Y537S、1例Y537N和2例Y537S/Y537N/D538G）。此外，使用1�例患者的纵向血浆样本评估治疗期间ESR1突变存在情况的变化。11例患者在治疗过程中出现cfDNA ESR1突变。11例MBC患者中有8例（72.7%）出现cfDNA ESR1突变，且为多克隆突变。
我们已证明35例MBC患者血浆与肿瘤组织中ESR1突变的独立分布情况。
