Background: The aim of the current study was to investigate the role of Circular RNA(circRNA) circASS1 in breast cancer(BC) cells, and this may be a novel therapy and a potential diagnostic biomarker or targeted treatment of BC. Methods: We analyzed the expression profile of human circRNAs in two BC cell lines: MCF-7, MDA-MB-231 by the circRNAs microarray, and we found the dysregulated circRNA: circASS1. Then the expression of circASS1 in breast cancer cells were identified. Next, measure of the abilities of invasion and migration were carried out by overexpressing circASS1 or silencing circASS1 in MDA-MB-231 and MCF-7, respectively. Luciferase Assay System were also carried out to detect harbored miRNA. Then, measure of the abilities of invasion and migration were carried out by overexpressing miR-4443 mimics. At last, the expression of circASS1's parental gene, ASS1 in gain-of-function and loss-of-function experiments were also quantitative analyzed. Results: Compared with MCF-7, the expression level of circASS1 in MDA-MB-231 is down-regulated. What is more, the results show overexpression of circASS1 could suppress invasion and migration in MDA-MB-231. On the contrary, silence of circASS1 could promote invasion and migration in MCF-7. miR-4443 could be captured by circASS1 according to Luciferase Assay System results, which could promote the ability of invasion and migration in MCF-7. Last, the expression of ASS1 is up-regulated in loss-of-function experiments, while down-regulated in gain-of-function experiments. Western blotting showed ASS1 up-regulated in loss-of-function experiments. Conclusions: CircASS1 suppresses invasion and migration capacity of BC cells by increasing expression of ASS1 and circASS1 could harbor miR-4443, suggesting that circASS1 could be a potential target in BC treatment and a prospective prognostic biological marker in BC.
Background: The biologic behavior of metaplastic breast cancer (MBC) has not been well elucidated due to its rarity and heterogeneity. This study was designed to assess the clinical and tumor characteristics and outcomes of MBC patients as compared with invasive ductal carcinoma (IDC) in general and the triple-negative (TN) subtype.Materials and methods: This study included 35 MBC and 2,839 IDC patients diagnosed at the National Cancer Center, Korea between 2000 and 2008. We, retrospectively, reviewed the clinicopathologic characteristics and clinical outcomes.Results: The mean age was 47.4 years for MBC group and 48.3 years for IDC group. The MBC group presented with larger tumors (≥ T2, 78.8% vs 41.0%; P<0.001), higher histologic grade (grade 3, 92.0% vs 44.6%; P<0.001), fewer ER and PgR positivity (ER+, 14.3% vs 69.0% ; P<0.001 and PgR+, 25.7% vs 66.1%; P<0.001), higher Ki-67 expression (35.5%±26.2% vs 20.6% ±19.8%; P=0.024) and more TN subtypes (48.6% vs 11.9%; P<0.001) than IDC group. Excluding de novo stage IV patients, 14 of 32 (43.7%) MBC patients and 260 of 2782 (9.4%) IDC patents developed disease recurrence with a median follow-up of 36.2 months (range, 4.9-117.8 months). MBC was a poor prognostic factor for disease recurrence in univariate and multivariate analysis (HR 5.19; 95% CI, 2.04-13.18; P=0.001). MBC patients demonstrated aggressive pathologic features and experienced more disease recurrence (HR 4.77; 95% CI, 1.99-11.44; P=0.001) even when compared with 330 patients with TN subtype.Conclusions:Patients with metaplastic breast carcinoma appeared to have inherent aggressive tumor biology with poorer clinical outcomes than those with IDC in general and TN subtype.Partly supported by NCC Grant No 0610240 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4057.
Background: Neoadjuvant chemotherapy(NAC) is now a relatively standard treatment for advanced breast cancer. Many reporters suggest that the response rate of NAC on ER/PR positive breast cancer is lower than on ER/PR negative cancer. However, there are few reports regarding the effectiveness of NAC according to expression of ER/PR. The aim of this study is to assess the effect of NAC on ER/PR weak positive breast cancer compared with ER/PR negative and strong positive breast cancer.Patients and Methods: 495 patients who underwent NAC between 2001 and 2008 were included. The patients were treated with variable chemotherapy regimens. We analyzed the response rate to NAC by revewing the preoperative breast imaging study including breast US and postoperative pathologic report. ER/PR expression by IHC were scored as negative, weak positive, intermediate and strong positive. We compared weak positive group with negative and strong positive group. We assessed clinicopathologic characteristics, response rate, disease progression according to ER/PR expression and chemotherapy regimens.Results: There were 165(33.3%) of ER/PR negative, 47(9.5%) of weak positive and 207(41.8%) of strong positive, respectively. Most of preoperative clinical stage was stage IIIA, 166(39.6%). Mean age of patients was 46.7±10.1 year. The pathologic complete response(pCR) was 47(11.2%). In weak positive group, pCR, partial response, stable disease, progressive disease was 9(19.1%), 23(48.9%), 9(19.1%) and 6(12.8%), respectively. There was no significant difference between weak positive group and negative group. However, pCR was less(11(5.3%)) in strong positive group compared with weak positive group. (p=0.004). In patients treated with preoperative anthracycline-based NAC and taxen-based NAC weak positive group was similar to negative group. However, pCR rate of strong positive group was lower than other groups.Conclusion: The clinicopathologic behaviors and effect of NAC on weak positive breast cancer were similar to ER/PR negative breast cancer. Therefore, neoadjuvant chemotherapy might be more effective in ER/PR weak positive breast cancer rather than strong positive breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4157.
Background: We aimed to evaluate the clinicopathologic factors affecting locoregional recurrence (LRR) in potentially operable breast cancer patients receiving preoperative systemic chemotherapy (PST).Methods: We reviewed the records of 316 breast cancer patients treated with PST (doxorubicin/cyclophosphamide, 101; docetaxel /capecitabine, 103; paclitaxel/gemcitabine, 43; doxorubicin/docetaxel, 69) followed by surgery and adjuvant radiotherapy between 2002 and 2006. The majority of patients had clinical positive axillary lymph nodes. To define the prognostic factors for LRR, age, clinical stage, hormone receptor (HR) and HER2 status, clinical and pathologic response, type of operation, pathological characteristics including tumor size, tumor grade, nodal status, number of positive axillary nodes, size of metastatic lymph node and status of resection margin and tumor multiplicity before and after PST were analyzed.Results: Overall 52 patients (16.5%) in the primary tumor and 87 patients (27.5%) in the axillary nodes achieved a pathologic complete response (pCR), and 206 patients (65.2%) underwent breast conserving surgery (BCS). With a median follow-up of 52.4 month (range: 4.7 - 89.4), total 18 (5.7%) patients developed LRR; 2 of 110 (1.8%) patients with mastectomy vs. 16 of 206 (7.7%) patients with BCS (p=0.04). Other significant factors in the univariate analysis were clinical T stage, HR status, clinical response and tumor multiplicity. A pCR in the primary tumor or node was not a prognostic factor for LRR in this study. In multivariate analysis, clinical T stage (T3/4, HR 7.8; 95% CI, 2.33-26.24; P=0.001), hormone receptor status (negative, HR 6.2; 95% CI, 1.91-20.22; P=0.002) and type of surgery (BCS, HR 9.5; 95% CI, 1.97-46.37; P=0.005) were independent prognostic factors. Among patients with BCS, advanced clinical T stage (HR 12.4; 95% CI, 3.45-44.56; P<0.001), negative hormone receptor (HR 4.74; 95% CI, 1.33-16.96; P=0.02), non-responding disease (HR 6.54; 95% CI, 1.07-40.12; P=0.04) and multiple tumors (HR 4.36; 95% CI, 1.06-17.90; P=0.04) developed more frequent LRR.Conclusions: Significantly more patients with advanced clinical T stage, negative HR status and BCS developed LRR in operable breast cancer treated with PST. Moreover, in patients with BCS after PST, clinically non-responding disease and multiple tumors showed unfavorable prognosis besides the larger tumors and negative hormone receptor.Partly supported by NCC Grant No 0610240 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1095.
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