Assessment of CPS + EG, Neo-Bioscore and Modified Neo-Bioscore in Breast Cancer Patients Treated With Preoperative Systemic Therapy: A Multicenter Cohort Study

Ling Xu, Yinhua Liu, Zhimin Fan, Zefei Jiang, Yunjiang Liu, Rui Ling, Jianguo Zhang, Zhigang Yu, Feng Jin, Chuan Wang, Shude Cui, Shu Wang, Dahua Mao, Bing Han, Tao Wang, Geng Zhang, Ting Wang, Baoliang Guo, Lixiang Yu, Yingying Xu, Fangmeng Fu, Zhenzhen Liu, Siyuan Wang, Ke Luo, Qian Xiang, Zhuo Zhang, Qianxin Liu, Bin Zhou, Zhaorui Liu, Chao Ma, Weiwei Tong, Jie Mao, Xuening Duan, Yimin Cui, Ling Xu, Yinhua Liu, Zhimin Fan, Zefei Jiang, Yunjiang Liu, Rui Ling, Jianguo Zhang, Zhigang Yu, Feng Jin, Chuan Wang, Shude Cui, Shu Wang, Dahua Mao, Bing Han, Tao Wang, Geng Zhang, Ting Wang, Baoliang Guo, Lixiang Yu, Yingying Xu, Fangmeng Fu, Zhenzhen Liu, Siyuan Wang, Ke Luo, Qian Xiang, Zhuo Zhang, Qianxin Liu, Bin Zhou, Zhaorui Liu, Chao Ma, Weiwei Tong, Jie Mao, Xuening Duan, Yimin Cui

Abstract

This study was to assess the prognosis stratification of the clinical-pathologic staging system incorporating estrogen receptor (ER)-negative disease, the nuclear grade 3 tumor pathology (CPS + EG), Neo-Bioscore, and a modified Neo-Bioscore system in breast cancer patients after preoperative systemic therapy (PST). A retrospective multicenter cohort study was conducted from 12 participating hospitals' databases from 2006 to 2015. Five-year disease free survival (DFS), disease specific survival (DSS), and overall survival (OS) were calculated using Kaplan-Meier Method. Area under the curve (AUC) of the three staging systems was compared. Wald test and maximum likelihood estimates in Cox proportional hazards model were used for multivariate analysis. A total of 1,077 patients were enrolled. The CPS + EG, Neo-Bioscore, and modified Neo-Bioscore could all stratify the DFS, DSS, and OS (all P < 0.001). While in the same stratum of Neo-Bioscore scores 2 and 3, the HER2-positive patients without trastuzumab therapy had much poorer DSS (P = 0.013 and P values < 0.01, respectively) as compared to HER2-positive patients with trastuzumab therapy and HER2-negative patients. Only the modified Neo-Bioscore had a significantly higher stratification of 5-year DSS than PS (AUC 0.79 vs. 0.65, P = 0.03). So, the modified Neo-Bioscore could circumvent the limitation of CPS + EG or Neo-Bioscore.

Clinical trial registration: ClinicalTrials.gov, identifier NCT03437837.

Keywords: CPS + EG; HER2; Neo-Bioscore; breast cancer prognosis; preoperative systemic therapy.

Conflict of interest statement

WT and JM were employed by Gennlife (Beijing) Technology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YX declared a shared affiliation, with no collaboration, with several of the authors (LX, YL, SW, SW, QX, ZZ, QL, BZ, ZL, CM, XD, YC) to the handling editor at the time of the review.

Copyright © 2021 Xu, Liu, Fan, Jiang, Liu, Ling, Zhang, Yu, Jin, Wang, Cui, Wang, Mao, Han, Wang, Zhang, Wang, Guo, Yu, Xu, Fu, Liu, Wang, Luo, Xiang, Zhang, Liu, Zhou, Liu, Ma, Tong, Mao, Duan and Cui.

Figures

Figure 1
Figure 1
Flow of participants.
Figure 2
Figure 2
Kaplan–Meier survival curves determined by CPS + EG in patients with breast cancer receiving preoperative systemic therapy (PST). (A) Disease free survival (DFS); (B) Disease specific survival (DSS); (C) Overall survival (OS).
Figure 3
Figure 3
Kaplan–Meier survival curves determined by Neo-Bioscore in patients with breast cancer receiving preoperative systemic therapy (PST). (A) Disease free survival (DFS); (B) Disease specific survival (DSS); (C) Overall survival (OS).
Figure 4
Figure 4
Kaplan–Meier survival curves for disease specific survival (DSS) determined by Neo Bioscore staging system for different HER2 status subgroup. Group 1: HER2-positive patients with trastuzumab therapy and HER2-negative patients; Group 2: HER2-positive patients without trastuzumab therapy. (A) DSS of different HER2 status subgroup in Neo-Bioscore scores 0 and 1; (B) DSS of different HER2 status subgroup in Neo-Bioscore score 2; (C) DSS of different HER2 status subgroup in Neo-Bioscore score 3; (D) DSS of different HER2 status subgroup in Neo-Bioscore scores 4, 5, and 6.
Figure 5
Figure 5
Kaplan–Meier survival curves for disease free survival (DFS) determined by the Neo-Bioscore staging system for different HER2 status subgroup. Group 1: HER2-positive patients with trastuzumab therapy and HER2-negative patients; Group 2: HER2-positive patients without trastuzumab therapy. (A) DFS of different HER2 status subgroup in Neo-Bioscore scores 0 and 1; (B) DFS of different HER2 status subgroup in Neo-Bioscore score 2; (C) DFS of different HER2 status subgroup in Neo-Bioscore score 3; (D) DFS of different HER2 status subgroup in Neo-Bioscore scores 4, 5, and 6.
Figure 6
Figure 6
Kaplan–Meier survival curves for overall survival (OS) determined by the Neo-Bioscore staging system for different HER2 status subgroup. Group 1: HER2-positive patients with trastuzumab therapy and HER2-negative patients; Group 2: HER2-positive patients without trastuzumab therapy. (A) OS of different HER2 status subgroup in Neo-Bioscore scores 0 and 1; (B) OS of different HER2 status subgroup in Neo-Bioscore score 2; (C) OS of different HER2 status subgroup in Neo-Bioscore score 3; (D) OS of different HER2 status subgroup in Neo-Bioscore scores 4, 5, and 6.
Figure 7
Figure 7
Kaplan–Meier survival curves determined by modified Neo-Bioscore in patients with breast cancer receiving preoperative systemic therapy (PST). (A) Disease free survival (DFS); (B) Disease specific survival (DSS); (C) Overall survival (OS).
Figure 8
Figure 8
Survival data assessed using the areas under the curves (AUCs) for the pretreatment clinical stage (CS), post-treatment pathological stage (PS), CPS + EG, Neo-Bioscore, and modified Neo-Bioscore. (A) Five-year disease free survival (DFS) assessed using AUCs in multiple staging systems; (B) Five-year disease specific survival (DSS) assessed using AUCs in multiple staging systems; (C) Five-year overall survival (OS) assessed using AUCs in multiple staging systems.

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