Concordance of Targeted Sequencing from Circulating Tumor DNA and Paired Tumor Tissue for Early Breast Cancer

Chi-Cheng Huang; Yi-Fang Tsai; Chun-Yu Liu; Pei-Ju Lien; Yen-Shu Lin; Ta-Chung Chao; Chin-Jung Feng; Yen-Jen Chen; Jiun-I Lai; Han-Fang Cheng; Bo-Fang Chen; Chih-Yi Hsu; Jen-Hwey Chiu; Ling-Ming Tseng

doi:10.3390/cancers15184475

Concordance of Targeted Sequencing from Circulating Tumor DNA and Paired Tumor Tissue for Early Breast Cancer

Cancers (Basel). 2023 Sep 8;15(18):4475. doi: 10.3390/cancers15184475.

Authors

Chi-Cheng Huang^{1

2

3}, Yi-Fang Tsai^{1

2

4}, Chun-Yu Liu^{1

4

5}, Pei-Ju Lien^{1

2}, Yen-Shu Lin^{1

2}, Ta-Chung Chao^{1

4

6}, Chin-Jung Feng^{1

2}, Yen-Jen Chen^{1

2

4}, Jiun-I Lai^{1

7

8}, Han-Fang Cheng^{1

2

4}, Bo-Fang Chen^{1

2}, Chih-Yi Hsu^{4

9}, Jen-Hwey Chiu^{1

2

10}, Ling-Ming Tseng^{1

2

4}

Affiliations

¹ Comprehensive Breast Health Center, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
² Division of Breast Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
³ Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10617, Taiwan.
⁴ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan.
⁵ Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
⁶ Division of Chemotherapy, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
⁷ Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
⁸ Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan.
⁹ Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan.
¹⁰ Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan.

Abstract

In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The liquid biopsy detection rate was 39% (all-stage breast cancers, n = 612). Among 246 early-stage patients assayed for both ctDNA and matched tumor, the cfDNA assay detected 73 (29.6%) and the comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (χ² test, p = 0.001). In total, 67 (25.6%) cases tested positive on both platforms, while the cfDNA and comprehensive assays detected an additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while the PIK3CA (39.4%), AKT1 (45.9%), and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers, considering that the concordance rate between tumor and liquid biopsy was only one-quarter.

Keywords: concordance; ctDNA; early-stage breast cancer; liquid biopsy; targeted sequencing; tumor sequencing.

Abstract

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