Tumor-stromal fibroblasts have recently been reported to play important roles in the tumor progression of cancer in various organs. The purpose of the present study was to investigate whether any characteristic histologic features of tumor-stromal fibroblasts could accurately predict the outcome of 318 patients with invasive ductal carcinoma of the breast who had received neoadjuvant therapy. We observed a small number of tumor-stromal fibroblasts with characteristic nuclear features existing in the tumor stroma and named these cells "atypical tumor-stromal fibroblasts." We then assessed the absence or presence of atypical tumor-stromal fibroblasts in biopsy (taken before neoadjuvant therapy) and surgical (taken after neoadjuvant therapy) materials and analyzed the outcome predictive powers of the presence of atypical tumor-stromal fibroblasts in biopsy and surgical materials using multivariate analyses that included well-known clinicopathological factors. The multivariate analyses demonstrated that the presence of atypical tumor-stromal fibroblasts assessed using biopsy materials had significantly higher hazard ratios for tumor recurrence and tumor-related death in patients with nodal metastasis and also significantly higher hazard ratios for tumor recurrence and tumor-related death independent of the hormone receptor status of the tumors. The results of this study clearly indicated that the presence of atypical tumor-stromal fibroblasts, especially in biopsy materials, is significantly associated with tumor recurrence and the tumor-related death of patients with invasive ductal carcinoma of the breast who have received neoadjuvant therapy.
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