Dataset Information

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

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.

SUBMITTER: Xu L

PROVIDER: S-EPMC8009183 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Xu Ling L Liu Yinhua Y Fan Zhimin Z Jiang Zefei Z Liu Yunjiang Y Ling Rui R Zhang Jianguo J Yu Zhigang Z Jin Feng F Wang Chuan C Cui Shude S Wang Shu S Mao Dahua D Han Bing B Wang Tao T Zhang Geng G Wang Ting T Guo Baoliang B Yu Lixiang L Xu Yingying Y Fu Fangmeng F Liu Zhenzhen Z Wang Siyuan S Luo Ke K Xiang Qian Q Zhang Zhuo Z Liu Qianxin Q Zhou Bin B Liu Zhaorui Z Ma Chao C Tong Weiwei W Mao Jie J Duan Xuening X Cui Yimin Y

Frontiers in oncology 20210316

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 ( ...[more]

PMID: 33796452

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Project description:ImportanceWe previously described and validated a breast cancer staging system (CPS+EG, clinical-pathologic scoring system incorporating estrogen receptor-negative disease and nuclear grade 3 tumor pathology) for assessing prognosis after neoadjuvant chemotherapy using pretreatment clinical stage, posttreatment pathologic stage, estrogen receptor (ER) status, and grade. Development of the CPS+EG staging system predated routine administration of trastuzumab in patients with ERBB2-positive disease (formerly HER2 or HER2/neu).ObjectiveTo validate the CPS+EG staging system using the new definition of ER positivity (≥1%) and to develop an updated staging system (Neo-Bioscore) that incorporates ERBB2 status into the previously developed CPS+EG.Design, setting, and participantsRetrospective review of data collected prospectively from January 2005 through December 2012 on patients with breast cancer treated with neoadjuvant chemotherapy at The University of Texas MD Anderson Cancer Center.Main outcomes and measurePrognostic scores were computed using 2 versions of the CPS+EG staging system, one with ER considered positive if it measured 10% or higher, the other with ER considered positive if it measured 1% or higher. Fits of the Cox proportional hazards model for the 2 sets of prognostic scores were compared using the Akaike Information Criterion (AIC). Status of ERBB2 was added to the model, and the likelihood ratio test was used to determine improvement in fit.ResultsA total of 2377 patients were included; all were women (median age, 50 years [range, 21-87 years]); ER status was less than 1% in 28.9%, 1% to 9% in 8.3%, and 10% or higher in 62.8%; 591 patients were ERBB2 positive. Median follow-up was 4.2 years (range, 0.5-11.7 years). Five-year disease-specific survival was 89% (95% CI, 87%-90%). Using 1% or higher as the cutoff for ER positivity, 5-year disease-specific survival estimates determined using the CPS+EG stage ranged from 52% to 98%, thereby validating our previous finding that the CPS+EG score facilitates more refined categorization into prognostic subgroups than clinical or final pathologic stage alone. The AIC value for this model was 3333.06, while for a model using 10% or higher as the cutoff for ER positivity, it was 3333.38, indicating that the model fits were nearly identical. The improvement in fit of the model when ERBB2 status was added was highly significant, with 5-year disease-specific survival estimates ranging from 48% to 99% (P < .001). Incorporating ERBB2 into the staging system defined the Neo-Bioscore, which provided improved stratification of patients with respect to prognosis.Conclusions and relevanceThe Neo-Bioscore improves our previously validated staging system and allows its application in ERBB2-positive patients. We recommend that treatment response and biologic markers be incorporated into the American Joint Committee on Cancer staging system.

Project description:BackgroundAccurately predicting outcomes for patients with breast cancer receiving neoadjuvant chemotherapy (NAC) is critical for clinical decisions. Prognostic models applicable to the Chinese population remain limited. The Neo-Bioscore staging system has been utilized as a predictive model for survival of breast cancer patients after NAC. This study aimed to validate the applicability of Neo-Bioscore in a Chinese population and develop an improved staging system based on it to predict prognosis of Chinese patients more accurately.MethodsThis study retrospectively collected clinicopathological and survival data in patients receiving NAC from February 2005 to August 2018 in PLA General Hospital. Discrimination, calibration and clinical usefulness were used to assess model performance. Univariate and multivariate analyses assessed relationships between clinicopathological factors and disease-specific survival. For model modification, postoperative pathological staging in the Neo-Bioscore was substituted with the posttreatment pathological tumor (ypT) stage and posttreatment pathological lymph node (ypN) stage. Neo-Bioscore and Modified Neo-Bioscore were compared with the American Joint Committee on Cancer (AJCC) staging system.ResultsA total of 436 patients with a median follow-up of 67 months were included. Five-year disease-specific survival (DSS), overall survival, and disease-free survival rates were 88.0%, 87.9%, and 76.8%, respectively. The concordance index (C-index) of the Neo-Bioscore staging system, posttreatment pathological stage (PS), and pretreatment clinical stage (CS) for DSS were 0.78 [95% confidence interval (CI): 0.72-0.83], 0.75 (95% CI: 0.69-0.82), and 0.68 (95% CI: 0.62-0.74), respectively. No significant difference between the Neo-Bioscore and PS was observed in the C-index (P=0.399). ypT and ypN were included in Neo-Bioscore to replace PS and create a modified staging system named MNeo-Bioscore. The C-index for DSS of the MNeo-Bioscore was 0.82 (95% CI: 0.78-0.87), and the calibration curve and decision curve analysis (DCA) curve performed well in internal validation.ConclusionsThe Neo-Bioscore staging system provided precise prognostic stratification for Chinese breast cancer patients receiving NAC; ypN and ypT stage may be substituted for PS to add significant prognostic value for Neo-Bioscore.

Project description:IntroductionPrevious studies verify the formation of enzymatically post-translationally modified (PTM) self-peptides and their preferred recognition by T cells in subjects with type 1 diabetes (T1D). However, questions remain about the relative prevalence of T cells that recognize PTM self-peptides derived from different antigens, their functional phenotypes, and whether their presence correlates with a specific disease endotype.MethodsTo address this question, we identified a cohort of subjects with T1D who had diverse levels of residual beta cell function. Using previously developed HLA class II tetramer reagents, we enumerated T cells that recognize PTM GAD epitopes in the context of DRB1*04:01 or PTM IA2 epitopes in the context of DQB1*03:02 (DQ8).ResultsConsistent with prior studies, we observed higher overall frequencies and a greater proportion of memory T cells in subjects with T1D than in HLA matched controls. There were significantly higher numbers of GAD specific T cells than IA2 specific T cells in subjects with T1D. T cells specific for both groups of epitopes could be expanded from the peripheral blood of subjects with established T1D and at-risk subjects. Expanded neo-epitope specific T cells primarily produced interferon gamma in both groups, but a greater proportion of T cells were interferon gamma positive in subjects with T1D, including some poly-functional cells that also produced IL-4. Based on direct surface phenotyping, neo-epitope specific T cells exhibited diverse combinations of chemokine receptors. However, the largest proportion had markers associated with a Th1-like phenotype. Notably, DQ8 restricted responses to PTM IA2 were over-represented in subjects with lower residual beta cell function. Neo-epitope specific T cells were present in at-risk subjects, and those with multiple autoantibodies have higher interferon gamma to IL-4 ratios than those with single autoantibodies, suggesting a shift in polarization during progression.DiscussionThese results reinforce the relevance of PTM neo-epitopes in human disease and suggest that distinct responses to neo-antigens promote a more rapid decline in beta cell function.

Dataset Information

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

Clinical trial registration

Publications

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

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