TY - JOUR
T1 - Copy number alteration is an independent prognostic biomarker in triple-negative breast cancer patients
AU - Nagahashi, Masayuki
AU - Ling, Yi Wei
AU - Toshikawa, Chie
AU - Hayashida, Tetsu
AU - Kitagawa, Yuko
AU - Futamura, Manabu
AU - Kuwayama, Takashi
AU - Nakamura, Seigo
AU - Yamauchi, Hideko
AU - Yamauchi, Teruo
AU - Kaneko, Koji
AU - Kanbayashi, Chizuko
AU - Sato, Nobuaki
AU - Tsuchida, Junko
AU - Moro, Kazuki
AU - Nakajima, Masato
AU - Shimada, Yoshifumi
AU - Ichikawa, Hiroshi
AU - Lyle, Stephen
AU - Miyoshi, Yasuo
AU - Takabe, Kazuaki
AU - Okuda, Shujiro
AU - Wakai, Toshifumi
N1 - Funding Information:
This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research Grant Number 22H03140 and 21K19522 for MN, and research funding from Denka for WT and SO.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to The Japanese Breast Cancer Society.
PY - 2023/7
Y1 - 2023/7
N2 - Background: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. Methods: A total of 47 patients with Stage I–III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. Results: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). Conclusions: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.
AB - Background: Next-generation sequencing (NGS) has enabled comprehensive genomic profiling to identify gene alterations that play important roles in cancer biology. However, the clinical significance of these genomic alterations in triple-negative breast cancer (TNBC) patients has not yet been fully elucidated. The aim of this study was to clarify the clinical significance of genomic profiling data, including copy number alterations (CNA) and tumor mutation burden (TMB), in TNBC patients. Methods: A total of 47 patients with Stage I–III TNBC with genomic profiling of 435 known cancer genes by NGS were enrolled in this study. Disease-free survival (DFS) and overall survival (OS) were evaluated for their association to gene profiling data. Results: CNA-high patients showed significantly worse DFS and OS than CNA-low patients (p = 0.0009, p = 0.0041, respectively). TMB was not associated with DFS or OS in TNBC patients. Patients with TP53 alterations showed a tendency of worse DFS (p = 0.0953) and significantly worse OS (p = 0.0338) compared with patients without TP53 alterations. Multivariable analysis including CNA and other clinicopathological parameters revealed that CNA was an independent prognostic factor for DFS (p = 0.0104) and OS (p = 0.0306). Finally, multivariable analysis also revealed the combination of CNA-high and TP53 alterations is an independent prognostic factor for DFS (p = 0.0005) and OS (p = 0.0023). Conclusions: We revealed that CNA, but not TMB, is significantly associated with DFS and OS in TNBC patients. The combination of CNA-high and TP53 alterations may be a promising biomarker that can inform beyond standard clinicopathologic factors to identify a subgroup of TNBC patients with significantly worse prognosis.
KW - Comprehensive genomic profiling
KW - Copy number alterations
KW - TP53
KW - Triple-negative breast cancer
KW - Tumor mutation burden
UR - http://www.scopus.com/inward/record.url?scp=85150185505&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85150185505&partnerID=8YFLogxK
U2 - 10.1007/s12282-023-01449-2
DO - 10.1007/s12282-023-01449-2
M3 - Article
C2 - 36930419
AN - SCOPUS:85150185505
SN - 1340-6868
VL - 30
SP - 584
EP - 595
JO - Breast Cancer
JF - Breast Cancer
IS - 4
ER -
