Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance

Zhe-Yu Hu; Ning Xie; Can Tian; Xiaohong Yang; Liping Liu; Jing Li; Huawu Xiao; Hui Wu; Jun Lu; Jianxiang Gao; Xuming Hu; Min Cao; Zhengrong Shui; Mengjia Xiao; Yu Tang; Qiongzhi He; Lianpeng Chang; Xuefeng Xia; Xin Yi; Qianjin Liao; Quchang Ouyang

EBioMedicine (Jun 2018)

Identifying Circulating Tumor DNA Mutation Profiles in Metastatic Breast Cancer Patients with Multiline Resistance

Zhe-Yu Hu,
Ning Xie,
Can Tian,
Xiaohong Yang,
Liping Liu,
Jing Li,
Huawu Xiao,
Hui Wu,
Jun Lu,
Jianxiang Gao,
Xuming Hu,
Min Cao,
Zhengrong Shui,
Mengjia Xiao,
Yu Tang,
Qiongzhi He,
Lianpeng Chang,
Xuefeng Xia,
Xin Yi,
Qianjin Liao,
Quchang Ouyang

Affiliations

Zhe-Yu Hu: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Central Laboratory, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Ning Xie: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Can Tian: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Xiaohong Yang: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Liping Liu: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Jing Li: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Huawu Xiao: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Hui Wu: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Jun Lu: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Jianxiang Gao: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Xuming Hu: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Min Cao: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Zhengrong Shui: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Mengjia Xiao: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Yu Tang: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China
Qiongzhi He: Geneplus-Beijing Institute, Beijing 102206, China
Lianpeng Chang: Geneplus-Beijing Institute, Beijing 102206, China
Xuefeng Xia: Geneplus-Beijing Institute, Beijing 102206, China
Xin Yi: Geneplus-Beijing Institute, Beijing 102206, China
Qianjin Liao: Geneplus-Beijing Institute, Beijing 102206, China
Quchang Ouyang: Hunan Cancer Hospital, and the Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha 410013, China; Department of Breast Cancer Medical Oncology, The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, Changsha 410013, China; Corresponding author at: Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya Medical School, Central South University, No. 283, Tongzipo Road, Changsha 410013, China.

Journal volume & issue: Vol. 32
pp. 111 – 118

Abstract

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Purpose: In cancer patients, tumor gene mutations contribute to drug resistance and treatment failure. In patients with metastatic breast cancer (MBC), these mutations increase after multiline treatment, thereby decreasing treatment efficiency. The aim of this study was to evaluate gene mutation patterns in MBC patients to predict drug resistance and disease progression. Method: A total of 68 MBC patients who had received multiline treatment were recruited. Circulating tumor DNA (ctDNA) mutations were evaluated and compared among hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) subgroups. Results: The baseline gene mutation pattern (at the time of recruitment) varied among HR/HER2 subtypes. BRCA1 and MED12 were frequently mutated in triple negative breast cancer (TNBC) patients, PIK3CA and FAT1 mutations were frequent in HR+ patients, and PIK3CA and ERBB2 mutations were frequent in HER2+ patients. Gene mutation patterns also varied in patients who progressed within either 3 months or 3–6 months of chemotherapy treatment. For example, in HR+ patients who progressed within 3 months of treatment, the frequency of TERT mutations significantly increased. Other related mutations included FAT1 and NOTCH4. In HR+ patients who progressed within 3–6 months, PIK3CA, TP53, MLL3, ERBB2, NOTCH2, and ERS1 were the candidate mutations. This suggests that different mechanisms underlie disease progression at different times after treatment initiation. In the COX model, the ctDNA TP53 + PIK3CA gene mutation pattern successfully predicted progression within 6 months. Conclusion: ctDNA gene mutation profiles differed among HR/HER2 subtypes of MBC patients. By identifying mutations associated with treatment resistance, we hope to improve therapy selection for MBC patients who received multiline treatment. Keywords: Circulating tumor DNA (ctDNA), Drug resistance, Gene mutation pattern, HR/HER2 subtype, Metastatic breast cancer, Progression-free survival

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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