Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast

Ji-Yeon Kim; Jong Han Yu; Seok Jin Nam; Seok Won Kim; Se Kyung Lee; Woong-Yang Park; Dong-Young Noh; Do-Hyun Nam; Yeon Hee Park; Wonshik Han; Jeong Eon Lee

doi:10.1016/j.tranon.2017.10.002

Genetic and Clinical Characteristics of Phyllodes Tumors of the Breast

Transl Oncol. 2018 Feb;11(1):18-23. doi: 10.1016/j.tranon.2017.10.002. Epub 2017 Nov 13.

Authors

Affiliations

¹ Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,06351, Korea.
² Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea.
³ Samsung Genome Institute, Samsung Medical Center, Seoul, 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Korea.
⁴ Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea.
⁵ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Korea; Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea; Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Korea.
⁶ Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Korea; Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Korea.
⁷ Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Korea. Electronic address: hanw@snu.ac.kr.
⁸ Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06351, Korea; Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University, Seoul 06351, Korea. Electronic address: jeongeon.lee@samsung.com.

Abstract

Purpose: Phyllodes tumors (PTs) of the breast are rare, accounting for less than 1% of all breast tumors. Among PTs, malignant PTs (MPTs) have malignant characteristics and distant metastases occur in about 20% to 30% of MPTs. However, there is no effective treatment for MPTs with distant metastasis, resulting in an abject prognosis. We performed targeted deep sequencing on PTs to identify the associations between genetic alterations and clinical prognosis.

Methods: We performed targeted deep sequencing to evaluate the genetic characteristics of PTs and analyzed the relationships between clinical and genetic characteristics.

Results: A total of 17 PTs were collected between 2001 and 2012. Histologic review was performed by pathologists. The samples included three benign PTs, one borderline PT, and 13 MPTs. The most frequently detected genetic alteration occurred in the TERT promoter region (70.6%), followed by MED12 (64.7%). EGFR amplification and TP53 alteration were detected in four MPTs without genetic alterations in MED12 and TERT promoter regions. Genetic alterations of RARA and ZNF703 were repeatedly found in PTs with local recurrence, and genetic alterations of SETD2, BRCA2, and TSC1 were detected in PTs with distant metastasis. Especially, MPT harboring PTEN and RB1 copy number deletion showed rapid disease progression.

Conclusions: In this study, we provide genetic characterization and potential therapeutic target for this rare, potentially lethal disease. Further large-scale comprehensive genetic study and functional validation are warranted.