Clinical Research Papers:
Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay
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Abstract
Kyunghee Park1,*, Moon Ki Choi2,*, Hae Hyun Jung3, In-Gu Do4, Kwang Hee Lee5, TaeJin Ahn1, Won Ho Kil6, Seok Won Kim6, Jeong Eon Lee6, Seok Jin Nam6, Duk-Hwan Kim7, Jin Seok Ahn2, Young-Hyuck Im2,3 and Yeon Hee Park2,3
1 Samsung Genomic Institute, Samsung Biological Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3 Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
4 Center of Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea
5 Life Science Solutions Group, Thermo Fisher Scientific Corporation, Seoul, Korea
6 Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
7 Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea
* These authors have contributed equally to this work
Correspondence to:
Yeon Hee Park, email:
Keywords: neoadjvant chemotherapy, pathologic complete response, breast cancer, refractory
Received: March 10, 2015 Accepted: May 02, 2015 Published: May 12, 2015
Abstract
Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes. This study was performed to identify actionable mutation(s) and to explain refractoriness and responsiveness to NAC. Included in this analysis were 76 patients among 397 with locally advanced breast cancer for whom a preoperative fresh-frozen paraffin-embedded tumor block was available for next-generation sequencing using AmpliSeq. The incidence of missense mutations in KRAS was much higher in patients with EF than in other groups (p < 0.01). In contrast, polymorphisms of the cMET gene were found in patients with pCR exclusively (p < 0.01).
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