TY - JOUR
T1 - Comprehensive molecular profiling broadens treatment options for breast cancer patients
AU - Kawaji, Hitomi
AU - Kubo, Makoto
AU - Yamashita, Nami
AU - Yamamoto, Hidetaka
AU - Kai, Masaya
AU - Kajihara, Atsuko
AU - Yamada, Mai
AU - Kurata, Kanako
AU - Kaneshiro, Kazuhisa
AU - Harada, Yurina
AU - Hayashi, Saori
AU - Shimazaki, Akiko
AU - Mori, Hitomi
AU - Akiyoshi, Sayuri
AU - Oki, Eiji
AU - Oda, Yoshinao
AU - Baba, Eishi
AU - Mori, Masaki
AU - Nakamura, Masafumi
N1 - Funding Information:
This work was supported by the Japan Society for the Promotion of Science KAKENHI (grant nos. 18J20301 and 18K08577). The authors thank Gabrielle White Wolf, PhD, and Sarah Williams, PhD, from Edanz Group ( https://en‐author‐services.edanzgroup.com/ac ) for editing a draft of this manuscript in English.
Funding Information:
MK has received honoraria as a speaker or in a consultant/advisory role from Chugai Pharmaceutical Co. (Tokyo, Japan). EB has received honoraria and a research grant from Chugai Pharmaceutical Co. The other authors declare no conflicts of interest.
Publisher Copyright:
© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
PY - 2021/1
Y1 - 2021/1
N2 - Precision oncology with next generation sequencing (NGS) using tumor tissue with or without blood has begun in Japan. Tumor molecular profiling tests are available, including the OncoGuide™ NCC Oncopanel System and FoundationOne® CDx (F1CDx). Our purpose was to identify potentially actionable genetic alterations in breast cancer with this comprehensive tumor profiling test. We enrolled 115 patients with pathologically diagnosed advanced or metastatic breast cancer. Comprehensive tumor genomic profiling, microsatellite instability, and tumor mutational burden (TMB) were determined using F1CDx. Testing was successful in 109/115 cases (94.8%). Clinically actionable alterations were identified in 76% of advanced breast cancer patients. The most frequent short variants were in TP53 (48.6%), PIK3CA (38.5%), GATA3 (11.0%), PTEN (11.0%), and BRCA1 (10.1%), and structural variants were in ERBB2 (24.8%), MYC (21.1%), RAD21 (21.1%), CCND1 (11.9%), FGF19 (10.1%), and PTEN (10.1%). Regarding human epidermal growth factor receptor (HER)2 status, 106/109 samples (97.2%) were concordant between F1CDx and HER2 testing with immunohistochemistry/fluorescence in situ hybridization. However, ERBB2 amplification was newly detected in four samples and ERBB2 mutations were detected in five HER2-negative breast cancer samples. Oncogenic BRCA mutations were found in three samples with F1CDx among 27 germline testing-negative samples. The mean TMB in all samples was 6.28 mut/Mb and tended to be higher in luminal B and triple-negative breast cancer (mean = 8.1 and 5.9 mut/Mb, respectively) compared with other subtypes. In conclusion, we established a system for precision oncology and obtained preliminary data with NGS as the first step. The information in this clinical sequencing panel will help guide the development of new treatments for breast cancer patients.
AB - Precision oncology with next generation sequencing (NGS) using tumor tissue with or without blood has begun in Japan. Tumor molecular profiling tests are available, including the OncoGuide™ NCC Oncopanel System and FoundationOne® CDx (F1CDx). Our purpose was to identify potentially actionable genetic alterations in breast cancer with this comprehensive tumor profiling test. We enrolled 115 patients with pathologically diagnosed advanced or metastatic breast cancer. Comprehensive tumor genomic profiling, microsatellite instability, and tumor mutational burden (TMB) were determined using F1CDx. Testing was successful in 109/115 cases (94.8%). Clinically actionable alterations were identified in 76% of advanced breast cancer patients. The most frequent short variants were in TP53 (48.6%), PIK3CA (38.5%), GATA3 (11.0%), PTEN (11.0%), and BRCA1 (10.1%), and structural variants were in ERBB2 (24.8%), MYC (21.1%), RAD21 (21.1%), CCND1 (11.9%), FGF19 (10.1%), and PTEN (10.1%). Regarding human epidermal growth factor receptor (HER)2 status, 106/109 samples (97.2%) were concordant between F1CDx and HER2 testing with immunohistochemistry/fluorescence in situ hybridization. However, ERBB2 amplification was newly detected in four samples and ERBB2 mutations were detected in five HER2-negative breast cancer samples. Oncogenic BRCA mutations were found in three samples with F1CDx among 27 germline testing-negative samples. The mean TMB in all samples was 6.28 mut/Mb and tended to be higher in luminal B and triple-negative breast cancer (mean = 8.1 and 5.9 mut/Mb, respectively) compared with other subtypes. In conclusion, we established a system for precision oncology and obtained preliminary data with NGS as the first step. The information in this clinical sequencing panel will help guide the development of new treatments for breast cancer patients.
UR - http://www.scopus.com/inward/record.url?scp=85097010534&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097010534&partnerID=8YFLogxK
U2 - 10.1002/cam4.3619
DO - 10.1002/cam4.3619
M3 - Article
C2 - 33274848
AN - SCOPUS:85097010534
SN - 2045-7634
VL - 10
SP - 529
EP - 539
JO - Cancer Medicine
JF - Cancer Medicine
IS - 2
ER -
