The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide(TC) compared with docetaxel, anthracycline, and cyclophosphamide(TEC) in neoadjuvant treatment of triple negative or HER2 positive breast cancer. Eligible breast cancer patients were randomized to receive six cycles of TC or TEC. The primary end point was pathological complete remission (pCR). Secondary end points included safety, clinical response rate, and survival outcome. One hundred and two patients were initially randomized and 96 patients were available for efficacy analysis. 96.9 % patients were treated with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 % (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20 (3–36) months, non-anthracycline-containing TC regimen treatment resulted in a worse event free survival (adjusted hazard ratio [HR] 2.42; 95 % CI1.11–5.30) and disease-free survival (HR 2.85; 95 % CI1.21–6.74) compared with TEC regimen, which was more apparent in triple negative subtype. Severe adverse event rates were similar, except that patients treated with TEC had a higher rate of neutropenia and leucopenia. TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting, especially in triple negative subtype, which deserves further validation.

Background: Breast cancer has become the most common malignant disease threatening women’s health. The cancer stem cell (CSC) has been recognized as a small subpopulation of cancer cells possesses stem cell properties, which is crucial in tumorigenicity, tumor invasion, drug resistance, and metastasis. The BCL11A plays a crucial role in breast cancer progression. To investigate the effect of BCL11A, a functional oncogene, we focused on its maintenance ability of stemness in breast cancer stem cells. Methods: We assessed the BCL11A expression level in tumor and non-tumor tissues using RT-qPCR and IHC. We subsequently established BCL11A-modulating breast cancer cell lines MDA-MB-231 and MCF-7. CCK8, colony formation assays, and xenograft model were used to determine the effect of BCL11A on tumorigenicity. Transwell assay and lung metastasis model in vivo were conducted to validate its function in metastasis. Its effect on stemness was assessed by flow cytometry and mammosphere formation. Western blot further characterized the importance of Wnt/β-catenin signaling in BCL11A-regulated cancer cell stemness. Results: A higher level of BCL11A was detected in clinical breast cancer samples. BCL11A promoted tumor formation, cancer cell mobility, spheroid forming, and epithelial-mesenchymal transition by activating the Wnt/β-catenin signaling. In addition, BCL11A was associated with lung metastasis and increased the breast cancer cells stemness. BCL11A high expression (BCL11A high ) cancer cells exhibited stem cell-like properties compared with BCL11A low cells, including a higher percentage of CD24 low /CD44 high subpopulation, self-renewal spheroids formation, and higher tumorigenicity. Our studies demonstrated that the Wnt/β-catenin signaling activated by BCL11A plays a potential role in the initiation of the renewal of breast cancer stem cells. Conclusions: BCL11A not only functions in breast cancer carcinogenesis but also enhanced the stemness of breast cancer through activating Wnt/β-catenin signaling, and may become a potential target for breast cancer treatment.

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Epithelial-mesenchymal transition (EMT) is a pivotal event in the progression of cancer towards metastasis. Given that pigment epithelium-derived factor (PEDF) inhibits angiogenesis, the present study analyzed whether PEDF expression is associated with EMT and prognosis in invasive ductal breast cancer (IDC). Immunohistochemical analysis was used to examine the expression levels of PEDF, E-cadherin, vimentin, Snail and nuclear factor-κB (NF-κB) in 119 cases of IDC. Correlations between PEDF expression and EMT-related genes, and clinicopathological features and clinical prognosis were analyzed. E-cadherin, vimentin, Snail and NF-κB expression was correlated with tumor size, lymph node metastasis and clinicopathological stage. PEDF expression was closely associated with tumor size. Spearman's rank correlation analysis revealed a positive correlation between PEDF and E-cadherin, vimentin, Snail and NF-κB expression (P<0.05). Additionally, Kaplan-Meier survival analysis demonstrated that the five-year survival rate was higher for patients with PEDF- and E-cadherin-positive tumors, but was lower for those with vimentin-, Snail- and NF-κB-positive tumors. Vimentin, E-cadherin and NF-κB levels were dependent prognostic factors of favorable outcomes in IDC, as determined by Cox multivariate analysis. PEDF expression in breast cancer was significantly associated with EMT-related genes, suggesting that it may be an EMT suppressor. However, its potential as a prognostic indicator in breast cancer warrants further investigation.

ObjectiveA previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide (TC) regimen was inferior to docetaxel, anthracycline and cyclophosphamide (TAC) in neoadjuvant treatment of triple-negative breast cancer (TNBC) and human epidermal growth factor receptor-2-(HER2)-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.MethodsTNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission (pCR). Secondary endpoints included clinical response rate, event-free survival (EFS), and overall survival (OS).ResultsA cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of 53 (range, 8–76) months, the patients achieving pCR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without pCR (P<0.05). TAC treatment resulted in consistently better EFS than TC treatment: the estimated 5-year EFS was 66.1% vs. 29.8% (P=0.002). Moreover, the estimated 5-year OS was also in favor of TAC: 88.4% vs. 51.6% (P<0.001). Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio (HR), 0.48; 95% confidence interval (95% CI), 0.26–0.90; P=0.021] and OS (HR, 0.20; 95% CI, 0.08–0.60; P=0.003). ConclusionsThe updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.