Abstract 3350: Cancer stem cells and lymph node metastasis in early stage breast cancer

Breast cancer is the leading cause of malignancy in women worldwide. Metastatic dissemination is the major cause of death. The mechanisms involved in cancer dissemination are unclear. The identification of tumor initiating cells in solid tumors has been reported. Initiating cells, also referred as cancer stem cells (CSCs), were defined as a CD44+/CD24— in breast carcinomas and have the ability to self-renewal, differentiate into any cell in the tumor and metastasize. The presence of CSCs is a suitable hypothesis for breast cancer metastasis and treatment failure. Nevertheless, there is no evidence of the relationship between CSCs in primary tumor and metastasis. Methods: we prospectively included 20 early-stage (I and II) breast cancer patients (17 invasive ductal carcinoma, 1 invasive lobular carcinoma, 1 metaplastic carcinoma and 1 tubular-lobular invasive carcinoma), and two patients with ductal carcinoma in situ (DCIS) subjected to primary surgery. The proportion of CSCs was analyzed in 22 primary tumors and in three lymph node metastasis by flow cytometry. Anti-human CD326 (EpCam; FITC), anti-human CD227 (MUC-1; FITC), anti-human CD44 (APC) and anti-human CD24 (PE) were used for phenotype analysis. The percentage of CD44+/CD24- cell population in primary invasive tumors was compared with standard prognostic factors. The mean age was 58.3 years (37 - 77), the mean pT was 1.8 cm (0.5 - 3.5), 13 patients (59%) had no axillary lymph node metastasis (NLN group) and 9 had positive axillary metastasis (PLN group) confirmed for standard histological evaluation. The ER, PR and HER2 positive expression rates were 84.2%, 78.9% and 15.7%, respectively. The Wilcoxon or Kruskal-Wallis tests were used for statistical analyses. Results: the percentage of CSCs in primary invasive ductal carcinoma (IDC) was 7.1% (0.2 - 29.4). In two DCIS we found 4.5% and 8.2% of CSCs. In lymph node metastases we observed a mean of 11.9% (1.5 - 31.1). In the other subtypes the mean percentage of CSCs was 12.7% (1.1 - 31.1). There was no association between CSC population in IDC and age (p= 0.8), pT (p= 0.7), tumor grade (p= 0.4), ER (p= 0.1), PR (p= 0.3) and HER2 (p= 0.4). We observed a significant increase in CSC population in PLN group [mean= 12.4% (4.1% - 29.4%)] when compared to patients without lymph node metastasis [mean= 2.4% (0.2% - 4.6%0] (p= 0.0008). Conclusion: this preliminary study indicates that the metastatic dissemination is associated with an increase in CSC population in early-stage breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3350.