Comparison of the performance of four staging systems in determining the prognosis of breast cancer among women undergoing neoadjuvant chemotherapy.

PURPOSE: Different tumor-related factors have been proposed to assess the risk of disease progression and death in women undergoing neoadjuvant breast cancer chemotherapy. Recently, besides the classical pre-treatment clinical stage (CS) and post-treatment pathologic stage (PS), estrogen receptor status and histologic grade (CPS + EG score) and HER2 results (Neo-Bioscore) have also been added to this suite of staging systems, generating new scores. The present study aims to compare the performance of these four staging systems, namely CS, PS, CPS + EG and Neo-Bioscore, in the prognosis of breast cancer in women undergoing neoadjuvant chemotherapy. METHODS: This study comprises a retrospective cohort study of female breast cancer patients diagnosed at the Brazilian National Cancer Institute, Brazil from January 2013 to December 2015. A descriptive analysis of patient characteristics was conducted, and Kaplan-Meier curves, a Cox proportional hazard analysis and Receiver Operating Characteristic (ROC) curves were developed according to the assessed staging system scores. RESULTS: A total of 803 patients were eligible for this study. Most were under 65 years old (88.0%), presented advanced tumors (clinical stage ≥ IIB 77.1%), with positive estrogen receptor (71.2%) and negative HER2 (75.7%) results. During the follow-up, 172 patients (21.4%) evolved to death. A statistical difference (p < 0.001) was observed between 5 year disease-free survival and 5 year overall survival rates according to the PS, CPS + EG and Neo-Bioscore staging systems. CONCLUSION: The PS, CPS + EG and Neo-Bioscore staging systems were proven to be equivalent to predict the prognosis of patients undergoing neoadjuvant chemotherapy.

Expression of epithelial-mesenchymal transition driver brachyury and status of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses to neoadjuvant chemotherapy of breast cancer.

Brachyury has been characterized as a driver of epithelial-mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no response = 2.6, partial response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant ( p = 0.62). We also observed a significant association between forkhead box protein 3 ( p = 0.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.

The Modified Neo-Bioscore System for Staging Breast Cancer Treated with Neoadjuvant Therapy Based on Prognostic Significance of HER2-Low Expression.

Background: Recently, the classification of HER2 status evolves from binary to ternary, and HER2-low expression may exhibit prognostic significance. We aimed to investigate whether HER2-low tumor is distinct from HER2-zero or HER2-positive tumors, and then to develop a modified staging system (mNeo-Bioscore) that incorporates HER2-low status into Neo-Bioscore. Patients and Methods: This cohort study was conducted using data from the prospective database on breast cancer patients between January 2014 and February 2019. Results: Among 259 patients enrolled in the study, the HER2-low tumor exhibited significantly lower histological grade, pathological staging and Ki-67 level than the other two groups. HER2-low patients and HER2-positive patients receiving concurrent HER2-directed therapy may have similar LRFS (p = 0.531) and OS (p = 0.853), while HER2-zero peers may have significantly worse LRFS (p = 0.006) and OS (p = 0.017). In particular, a similar trend was also found in the patients without pathological complete response after surgery. Incorporation of HER2-low status made improvement in fit: 5-year OS rate estimates ranged from 33.33% to 100% for mNeo-Bioscore vs 61.36% to 100% for Neo-Bioscore. Conclusions: This study demonstrated that HER2-low tumor may exhibit prognostic significance. The innovative mNeo-Bioscore, based on a new classification of HER2 status, may serve as a prognostic staging system superior to Neo-Bioscore.

Evaluation of the relationship between Ki67 expression level and neoadjuvant treatment response and prognosis in breast cancer based on the Neo-Bioscore staging system.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is widely used in the treatment of primary breast cancer. Different staging systems have been developed to evaluate the residual tumor after NAC and classify patients into different prognostic groups. Ki67, a proliferation marker, has been shown to be useful in predicting treatment response and prognosis. We aimed to investigate the prognostic importance Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels in breast cancer patients who received NAC and correlations between Neo-Bioscore stage and pretreatment and posttreatment Ki67 levels. METHODS: A total of 176 invasive breast carcinoma patients who underwent NAC were included in the study. Ki67 levels were evaluated by immunohistochemical methods in Trucut biopsy and surgical excision specimens. Patients were classified into prognostic groups using the Neo-Bioscore staging system. RESULTS: Patients with high pretreatment Ki67 score were more likely to be in the higher Neo-Bioscore risk group (p < 0.001). Patients with a high posttreatment Ki67 score were more likely to be in the higher Neo-Bioscore prognostic risk group (p < 0.001). Overall survival (OS) and disease-free survival (DFS) were shorter in patients with high posttreatment Ki67 scores and in patients in the higher Neo-Bioscore risk group. We also determined a cutoff 37% for pathological complete response. CONCLUSION: Neo-Bioscore staging system is found to be important in predicting survival. The posttreatment Ki67 level is more important than pretreatment Ki67 level in predicting survival.

External verification and improvement of the Neo-Bioscore staging system in a Chinese cohort.

Background: Accurately 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. Methods: This 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. Results: A 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. Conclusions: The 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.

Neo-Bioscore in Guiding Post-surgical Therapy in Patients With Triple-negative Breast Cancer Who Received Neoadjuvant Chemotherapy.

AIM: Patients with triple-negative breast cancer (TNBC) who have not achieved pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) were considered for adjuvant capecitabine. This study was to explore the utility of the Neo-Bioscore in guiding post-surgical therapy in TNBC. PATIENTS AND METHODS: The Neo-Bioscore was calculated for patients with non-metastatic primary breast cancer who received NAC at National Cancer Center Hospital East, Japan. RESULTS: A total of 329 patients were evaluated. The Neo-Bioscore stratified prognosis after NAC better than clinical or pathological stage. The Neo-Bioscore performed well in the selection of patients with TNBC with excellent prognoses despite non-pCR; no death was observed in patients who had a Neo-Bioscore of 2, the lowest score in those with TNBC. CONCLUSION: The Neo-Bioscore can improve the prognostic stratification of patients after NAC for breast cancer over clinical and pathological staging and may enable the identification of patients with non-pCR TNBC who can avoid additional adjuvant chemotherapy.

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

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.

Validation of CPS+EG, Neo-Bioscore, and modified Neo-Bioscore staging systems after preoperative systemic therapy of breast cancer: Protocol of a retrospective multicenter cohort study in China.

Prognostic assessment after preoperative systemic therapy (PST) is critical to develop a therapeutic strategy for breast cancer management. Currently, a clinical-pathologic staging system that incorporates ER status and nuclear grading (CPS + EG), and the Neo-Bioscore system that includes HER2 status into CPS + EG, are used to predict outcomes in patients with breast cancer after PST. While HER2-positive is recognized as a favorable factor in the Neo-Bioscore system based on results in patients administered one year of trastuzumab as anti-HER2 therapy, most HER2-positive cases have difficulty accessing anti-HER2 treatment in China. Therefore, it is crucial that a modified Neo-Bioscore staging system is developed that incorporates an additional factor of poor prognosis, HER2-positive status without trastuzumab treatment, to determine accurate prognosis. We propose a retrospective multicenter cohort study in China to validate CPS + EG, Neo-Bioscore, and the modified Neo-Bioscore system and determine the accuracy of prediction. Primary breast cancer patients without metastasis treated with PST and surgery in academic institutions or hospitals of provincial level in China will be included. Disease-free, disease specific, and overall survival will be calculated using the Kaplan-Meier Method, stratified by CPS + EG, Neo-Bioscore, and the modified Neo-Bioscore staging system. Areas under the curve of each staging system will be calculated. Multivariate analysis using Wald testing and maximum likelihood estimates in a Cox proportional hazards model will be conducted.