-Original-

Use of Liquid Biopsy to Detect PIK3CA Mutation in Metastatic Breast Cancer

Maki Nakai¹, Takeshi Yamada², Kenta Sekiya¹, Ai Sato¹, Meishi Hankyo¹, Sho Kuriyama², Goro Takahashi², Tomoko Kurita¹, Keiko Yanagihara³, Hiroshi Yoshida², Ryuji Ohashi⁴ and Hiroyuki Takei¹

¹Department of Breast Surgery and Oncology, Nippon Medical School Hospital, Tokyo, Japan
²Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School Hospital, Tokyo, Japan
³Department of Surgery, Nippon Medical School Tama Nagayama Hospital, Tokyo, Japan
⁴Department of Integrated Diagnostic Pathology, Nippon Medical School, Tokyo, Japan

Background: PIK3CA is associated with tumor progression, and the prevalence of PIK3CA mutation is high in breast cancer. Liquid biopsy offers convenient, noninvasive, and real-time insight into genetic alteration. In this study, we used liquid biopsy to detect PIK3CA mutations in patients with breast cancer.
Methods: We recruited patients with histologically confirmed breast cancer and distant metastases between April 2020 and September 2020. Circulating DNA was extracted from plasma (ctDNA) and exosomes (exoDNA). PIK3CA mutations (exons 9 and 20) were analyzed by droplet digital PCR.
Results: Of the 52 patients recruited, 16 had PIK3CA mutations in tumor tissue or blood: 9 had exon 9 mutations (E542K and E545K) and 8 had exon 20 mutations (H1047 L and H1047R). In 8 (15%) of the 52 patients, PIK3CA mutations were detected by liquid biopsies using ctDNA in 5 (9%), exoDNA in 6 (11%), and both ctDNA and exoDNA in 3 (6%). Of the 8 patients with PIK3CA mutations detected by liquid biopsies, 3 had no PIK3CA mutations in the primary tumors.
Conclusions: PIK3CA mutations can be detected by liquid biopsy even in patients with no PIK3CA mutations in their primary tumors; thus, combination analysis using tissue and liquid biopsies can provide clinically useful information for patients with breast cancer.

J Nippon Med Sch 2022; 89: 66-71

Keywords
breast cancer, liquid biopsy, genetic screening

Correspondence to
Takeshi Yamada, Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan
y-tak@nms.ac.jp

Received, December 10, 2020
Accepted, February 3, 2021