Abstract P4-09-12: A prospective evaluation of comprehensive tumor profiling busing a targeted Next-generation sequencing for Japanese breast cancer patients
Authors: Kawaji Hitomi , Kubo Makoto , Yamashita Nami , Harada Yurina , Shimazaki Akiko , Hayashi Saori , Kurata Kanako , Yamada Mai , Kaneshiro Kazuhisa , Kai Masaya , Baba Eiji , Oda Yoshinao , Nakamura Masafumi 
Published: March 2020

Abstract
Background: Oncogenic genetic alterations leading to identify patients who may benefit from the target therapy are essential biomarkers for them, and to review widely what kind of driver gene alteration that each cancer has is important for effective cancer treatments. Next-generation sequencing (NGS) is a powerful tool to comprehensively analyze driver gene mutations. In Japan, some multiplex cancer genetic testings were covered from national health insurance from June, 2019. Therefore, we reviewed our data using a targeted NGS platform (FoundationOne CDx (F1CDx)) in Japanese breast cancer patients.
Methods: This study included 105 local advanced or metastatic breast cancer patients in Kyushu University Hospital between October 2018 and June 2019. We prospectively assessed NGS results, clinical characteristics and therapies received for the patients. Primary endpoint was a frequency at which actionable genetic alterations were detected, and coprimary secondary endpoints were the sequence success rate, the rate at which the corresponding therapeutic agent was administered, the percentage of agreement to results with approved in vitro diagnostic agents, and the overall survival. This study was approved by the Institutional Review Board of our hospital (No. 758-00).
Results: Samples from 105 breast cancer patients were tested, all of who were women. Then, 99 samples (94.3 %) were success for sequencing and 6 (5.7 %) were failure. Among the succeeded samples, tested from primary tumor is 71 (71.7 %) and metastasis is 34 (34.3 %), while 62 (62.6 %) were biopsied tumor specimen and 43 (37.4 %) resected. The clinical subtypes of them were 45 HR +/ HER2 - (45.5 %), 22 HER2+ (22.2 %), and 32 TNBC (32.3 %).
Based on the biomarker findings from F1CDx, microsatellite statuses in 97 samples were stable and 1 sample high, who was diagnosed with Lynch syndrome. Regarding tumor mutation burden (TMB), of 98 patients, 3 had high TMB (&gt;19 mutations/mb), 31 had intermediate TMB (6-19 mutations/mb), 63 had low TMB (1-5 mutations/mb) and 1 were unable to be determinated. The average was 6.7 mutations/mb. The most frequent alteration is TP53 (54.5 %), PIK3CA (39.4 %) and ERBB2 (29.3 %). 87 patients (87.8 %) detected the alterations leading to some therapeutic options based on genetic profiling.
25 patients with metastases had taken genetic testing for BRCA1/2 germline mutation (gBRCA1/2mut), which isnamed BRACAnalysis. In all of 5 patients who had gBRCA1/2muts the same spot mutations were also detected with F1CDx. In 2 of 20 patients had negative gBRCA1/2mut, somatic BRCA1/2muts were newly detected with F1CDx. In 9 of the other patients had not taken the genetic testing, somatic BRCA1/2muts were founded.
18 tumors with HER2/Immunohistochemical staining (IHC) =3+ were judged as ERBB2 amplification, 3 tumors with HER2/IHC=2+ and HER2/FISH positive as low amplification, and 18 tumors with HER2/IHC=2+ and HER2/FISH negative as no amplification. Moreover, there are were 3 patients who newly confirmed ERBB2 amplification and 4 patients who confirmed ERBB2 mutations in this study.
Conclusions: The multiplex cancer genetic testing could help identify actionable alterations for the breast cancer patients. NGS results may add some new therapeutic options to standard therapies.
Citation Format: Hitomi Kawaji, Makoto Kubo, Nami Yamashita, Yurina Harada, Akiko Shimazaki, Saori Hayashi, Kanako Kurata, Mai Yamada, Kazuhisa Kaneshiro, Masaya Kai, Eiji Baba, Yoshinao Oda, Masafumi Nakamura. A prospective evaluation of comprehensive tumor profiling busing a targeted Next-generation sequencing for Japanese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-12.