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Abdel-Fatah, TM; Ball, G; Lee, AHS; Pinder, S; MacMilan, RD; Cornford, E; Moseley, PM; Silverman, R; Price, J; Latham, B; Palmer, D; Chan, A; Ellis, IO; Chan, SYT (2015)
Publisher: American Association for Cancer Research
Languages: English
Types: Article
Subjects:
Purpose: There is a need to identify more sensitive clinico-pathological criteria to assess the response to Neo-ACT and guide subsequent adjuvant-therapy. Experimental Design: We performed a clinico-pathological assessment of 427 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 5-years. Patients were divided into a training set treated with anthracycline combination chemotherapy (AC, n=172); an internal validation set treated with AC and taxane (n=130); and an external validation set treated with AC with or without taxane (n=125). Results: A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lympho-vascular invasion, and increasing number of lymph node metastases were significantly associated with short disease-free survival (DFS) and breast-cancer specific survival (BCSS, p<0.01), whilst reduction of tumour size was associated with DFS (p=0.022). Nottingham Clinico-Pathological Response Indexes (NPRIs) were calculated and four prognostic groups (NPRI-PGs) were identified. Patients in prognostic group 2 (NPRI-PG2) for DFS (n=63/172; 36.6%) and BCSS (66/172; 38.4%) have the same prognosis as those who achieved pCR (NPRI-PG1; 15%). Receiver operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding NPRI improved their performance as a predictor for both DFS (AUC=0.87) and BCSS (AUC= 0.88). Conclusions: The NPRI predicts DFS and BCSS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinico-pathological response as a study end-point, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers.
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