Analysis of 246 sentinel lymph node biopsies of patients with clinical primary breast cancer by application of carbon nanoparticle suspension.

AIM: This study aims to explore the accuracy, specificity and laws of axillary lymph node metastasis predicted by sentinel lymph node biopsy (SLNB) by comparing axillary lymph node status via SLNB and axillary lymph node dissection (ALND) with nanocarbon as the tracer. METHODS: Forty six patients were retrospectively analyzed. These patients underwent SLNB with nanocarbon as the tracer from March 2013 to April 2014. RESULTS: Two hundred and forty six patients of sentinel lymph node (SLN) were successfully detected. Among these patients, 8 patients had 1 SLN (3.25%), 33 patients had 2 SLN (13.41%), 46 patients had 3 SLN (18.70%), 51 patients had 4 SLN (20.73%), 40 patients had 5 SLN (16.26%), 24 patients had 6 SLN (9.76%) and 24 patients had 7 or more SLN (9.76%). The SLNB success rate of nanocarbon staining in the 246 cases was 99.59%, accuracy rate was 97.06% and sensitivity was 93.22%. Furthermore, false negatives were found in four patients, and the false-negative rate was 6.78%. The number of lymph node metastasis in the SLNB and ALND of early-stage breast cancer was analyzed. When the number of SLN dissection was 1, 2, 3, 4, 5, 6 or 7, the coincidence rate of lymph node metastasis for SLNB and ALND was 80.00, 84.36, 78.57, 88.89, 90.48, 80.00, 73.68 and 78.36, respectively. CONCLUSION: Sentinel lymph node biopsy performed using the nanocarbon staining method is simple, easy and reliable, and it can be used to predict the axillary status of breast cancer in the early stage.

miR-29a regulated ER-positive breast cancer cell growth and invasion and is involved in the insulin signaling pathway.

Increasing amounts of evidence show that insulin can activate different insulin signaling pathways to promote breast cancer growth and invasion. miR-29a plays crucial roles in decreasing glucose-stimulated insulin secretion, as well as in regulating breast cancer cell proliferation and EMT. However, the mechanism responsible for the regulatory effects of miR-29a on breast cancer growth and invasion and the relationship between these effects and insulin signaling remains unclear. Herein, we showed that human insulin increased miR-29a expression in ER-positive breast cancer cells and that miR-29a facilitated the ability of insulin to promote breast cancer cell proliferation and migration. We found that miR-29a-induced cell proliferation and metastasis acceleration occurred primarily through ERK phosphorylation. The IGF-1R is the upstream target gene of miR-29a, while CDC42 and p85α are the downstream target genes of miR-29a. These results have provided us with information regarding the molecular mechanisms by which hyperinsulinemia promotes breast cancer occurrence and development and thus leads to a poor prognosis in breast cancer patients and indicate that miR-29a plays an important role in breast cancer development and invasion.

miR-34a expression in human breast cancer is associated with drug resistance.

miR-34a is significantly down-regulated in breast cancer tissues and cell lines, which may be correlated with breast cancer multi-drug resistance (MDR). Here, we conducted cell-based experiments and clinical studies in a cohort of 113 breast cancer samples to analyze miR-34a expression and breast cancer MDR. Expression of miR-34a is down-regulated in the multi-drug resistant MDR-MCF-7 cells compared with its parental cells. Patients with miR-34a low expression had poorer overall survival (OS) and disease free survival (DFS) in comparison with those with high expression. Transfecting miR-34a mimics into MDR-MCF-7 breast cancer cells led to partial MDR reversal. Compared with the control group, miR-34a significantly reduced both the mRNA and protein expressions of BCL-2, CCND1 and NOTCH1, but no obvious changes were found in P53 or TOP-2a expression. In breast cancer tissue samples, the expression of miR-34a was related to BCL-2, CCND1 and NOTCH1, but not to HER-2, P53 and TOP-2a. Altogether, our findings suggest that miR-34a is an MDR and prognosis indicator of breast cancer, which may participate in the regulation of drug-resistant breast cancer by targeting BCL-2, CCND1, and NOTCH1.

Interleukin-12 activated CD8+ T cells induces apoptosis in breast cancer cells and reduces tumor growth.

During the past two decades, cytokines have emerged as key molecules to modulate innate and adaptive immunity and mediate anti-tumor activity. Although multiple cytokine types are implicated for such anti-tumor activity in several cancer types, it remains largely unknown in breast cancer. In this study, cytokines that are prior known for antitumor activity in different cancer types were examined against breast cancer using a 4T1 cells based xenograft-model. Our results showed Interleukin-12 (IL-12) (500ng/mouse) significantly suppressed the growth of tumors, while other cytokines showed minimal suppression. Subsequent molecular analysis by flow cytometry and immunohistochemistry confirmed the CD8+ cells infiltration and Interferon-γ (IFN-γ) production by them in tumor environment. In addition, we observed that IFN-γ production by activated CD8+ cells directly induced apoptosis in tumor cells, which together indicate that IL-12 causes CD8+ cells to infiltrate and secrete IFN-γ in tumor environment, which induce apoptosis in them and causes tumor growth suppression. Furthermore, we showed that lower dosage of IL-12 and chemotherapy drug tamoxifen combinations enhanced the tumor suppression as opposed to single treatments, and thereby propose an alternate option for high dosage associated effects for both drug and cytokine treatments.

Luminal B breast cancer: patterns of recurrence and clinical outcome.

In recent years, most studies on breast cancer relapse and metastasis have focused on non-luminal breast cancers (including the basal-like and HER-2 subtypes) because of their poor prognosis. However, the luminal B subtype is more common, but this type has not been investigated as thoroughly. In the current study, we collected data on 258 patients with luminal-B breast cancer patients with recurrence and metastasis served as the observation group, and 189 patients with non-luminal breast cancer during the same period served as the control group. This study aimed to investigate the pattern of recurrence and clinical outcome after follow-up treatment for luminal B breast cancer. We found a higher proportion of local recurrence and single bone metastasis in patients with luminal B breast cancer than in patients in the non-luminal groups. The risk of recurrence and metastasis in patients with luminal B breast cancer during a 2- to 5-year period and after 5 years was still present, but the risk in patients with non-luminal breast cancers had obviously decreased during the same period. Patients with luminal B breast cancer with recurrence or/and metastasis had a better prognosis after reasonable treatment. The recurrence patterns and clinical outcomes of patients with luminal B breast cancer according to HER2 status were also different, to some degree. These results are of potential clinical relevance especially for the monitoring of clinical prognosis and targeted therapy intervention for luminal B breast cancer.

[Correlation between Tau expression and clinicopathological characteristics of breast invasive ductal carcinomas].

OBJECTIVE: To explore the expression of Tau protein in breast invasive ductal carcinomas and examine the correlation between its expression and clinicopathological characteristics of breast cancer. METHODS: The clinicopathological data of 150 breast cancer patients at Third Municipal Hospital from October 2007 to June 2011 were collected and analyzed. Immunohistochemical method was used to detect the expressions of estrogen receptor (ER), progesterone receptor (PR), HER-2 and Tau protein. RESULTS: No correlations existed between the expression of Tau protein and age, tumor size or node metastasis of breast cancer patients (χ(2) = 0.02, P = 0.88; χ(2) = 0.55, P = 0.46; χ(2) = 1.02, P = 0.31). The expressions of Tau in ER positive patients were significantly higher than ER negative patients. And this trend extended to PR positive and HER-2 negative patients (χ(2) = 15.77, P = 0.00; χ(2) = 5.03, P = 0.03; χ(2) = 8.00, P = 0.01). The expression of Tau protein in Luminal A subtype was significantly higher than in Luminal B subtype, HER-2 over-expression subtype and basal like subtype (χ(2) = 7.26, P = 0.01). CONCLUSIONS: Over-expressed in breast cancer, Tau protein is associated with ER, PR and HER-2. However, the relation between Tau protein and prognosis of breast cancer requires further researches.

Tau proteins expressions in advanced breast cancer and its significance in taxane-containing neoadjuvant chemotherapy.

Tau is a microtubule-associated protein and expressed in normal breast epithelial cells and breast cancer. Tau expression in breast cancer may be important for chemotherapy optimization. This study is to investigate the expression of Tau in advanced breast cancer and its significance in taxane-containing neoadjuvant chemotherapy. Levels of Tau protein in advanced breast cancer were detected immunohistochemically. The chemotherapeutic efficacy indexes in Tau(-) group, which includes the remission rate, Miller-Payne pathological reactive grade, and pathologic complete response rate, were improved compared with that in Tau(+) group. There was difference in the efficacy indexes among ER+ subgroups but not among ER- patients. In addition, Tau expression was positively correlated (r = 0.32, P < 0.00). In multivariate analysis, when age, clinical stage, postoperative lymph node metastasis, ER, PR, HER2, Ki-67, TP53, or Tau status were included, postoperative lymph node metastasis and Tau-negative status were identified as independent predictors of pathologic complete response. In conclusion, negative Tau protein expression may be an effective predictor for taxane-containing neoadjuvant chemotherapy, especially in ER+ subgroups. Further study on the molecular mechanism and utility of Tau for individualizing adjuvant chemotherapy is warranted.