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Supplementary Figure 4. Multivariable Cox proportional hazards regression analyses for disease free survival (DFS; left panel) and corresponding forest plots (Right panel).

Supplementary Figure 2. Receiver operating characteristic (ROC) analysis of pathological complete response (pCR), revised pathological TNM stage (yp-TNM stage), Clinical-Pathologic Scoring System (CPS) score and CPS-Oestrogen receptor-histological grade (CPS-EG) were performed for predicting breast cancer specific survival in the training (A), internal validation (B), external validation (C) and combined three cohorts (D).

supplemental figure legend.

Supplementary Figure 5. Kaplan Meier curves and lifetime table showing disease free survival (DFS) in the training (A), internal validation (B), and external validation (C) cohorts stratified according to Nottingham clinicopathological response index prognostic groups (NPRI-PGs).

Supplementary Figure 1. Kaplan Meier curves showing disease free survival (DFS) in the training (upper panels), internal validation (middle panels) and external validation (lower panels) cohorts stratified according to the number of lymph node (LN) metastases (i), presence of lympho-vascular invasion (LVI; ii), absence of fibrosis (iii) the percentage reduction in primary tumour size (iv).

Supplementary Tables 1 to 5. Table (S1): Clinico-pathological characteristics of all three individual cohorts and the sum of all three together. Table (S2): Summery of pathological features that have been reviewed Table (S3): Univariate and multivariate backward step-wise analysis for factors associated with disease free survival (DFS) in the training cohort. Table (S4): Summery of the code system that has been used for calculation of Nottingham clinico-pathological response index (NPRI) Table (S5): Univariate analysis for clinicopathological features associated with disease free survival (DFS) and breast cancer specific survival (BCSS) in the training, internal and external validation cohorts.

Purpose: There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy.Experimental Design: We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125).Results: A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer–specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87).Conclusions: The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers. Clin Cancer Res; 21(5); 1052–62. ©2014 AACR.

Supplementary Figure 3. Multivariable Cox proportional hazards regression analyses for disease free survival (DFS; left panel) and corresponding forest plots (Right panel).

Supplementary Figure 6. Receiver operating characteristic (ROC) analysis of Nottingham clinico-pathological response index (NPRI) score and other clinico-pathological covariates were performed for predicting disease free survival in the training (A), internal validation (B), external validation (C) and combined three cohorts (D).