Effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel in vitro and vivo.

NIMA-related kinase 2B has been known to be an important centrosome regulatory factor. The aim of this study was to investigate the effect of NIMA-related kinase 2B on the sensitivity of breast cancer to paclitaxel. We detected the expression of NIMA-related kinase 2B messenger RNA in MCF-10 cells, including MCF-10A, MCF-10AT, MCF-10DCIS.com , and MCF-10CA1a. The influence of NIMA-related kinase 2B in nude mouse was also detected. The association between NIMA-related kinase 2B and clinicopathological factors was explored in invasive ductal carcinoma tissues. NIMA-related kinase 2B was lowly expressed in the precancerous cells, MCF-10A and MCF-10AT, and it was highly expressed in carcinomatous cells, MCF-10DCIS.com and MCF-10CA1a. The upregulation of NIMA-related kinase 2B can introduce the growth of MCF-10AT cells, knockdown of NIMA-related kinase 2B could remarkably inhibit cell proliferation in MCF-10DCIS.com and MCF-10 CA1a cells. Comparing the volume of the xenografts in nude mouse, we found that the tumors treated by NIMA-related kinase 2B small interfering RNA associated with paclitaxel were the smallest among all the groups. Expression of NIMA-related kinase 2B messenger RNA was associated with higher histological grades, positive lymph node, and high Ki67 index (>20%). The partial response rates were 75.0% in NIMA-related kinase 2B negative (NIMA-related kinase 2B-) patients and 15.8% in NIMA-related kinase 2B++ patients. The progressive disease rates were 10.0% in NIMA-related kinase 2B- patients and 52.6% in NIMA-related kinase 2B++ patients ( p = 0.002). Our findings suggested that NIMA-related kinase 2B could play a role in the development and progression of breast cancer. Combination treatment using NIMA-related kinase 2B small interfering RNA and paclitaxel might be a novel potential therapy method for breast cancer.

An associated classification of triple negative breast cancer: the risk of relapse and the response to chemotherapy.

BACKGROUND: Triple negative breast cancer (TNBC) is heterogeneous and considered as an aggressive tumor. This study was to evaluate the associated classification and its correlations with prognosis and the response to chemotherapy in Chinese women. METHODS: Four hundred and twenty-eight cases of invasive TNBC were involved in this study. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 (CK5/6), Ki67 and p53 were analyzed by immunohistochemistry and compared with patient outcome, and its implications and chemotherapy response were evaluated in four subgroups: typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC), non-specific invasive ductal carcinoma (IDC) and other types. RESULTS: The factors of tumor grade, tumor stage, lymph node status, EGFR/CK5/6 status and p53 labeling index were different among the groups. TMC tumors had the lowest rate of relapse (5.8%), while AMC, IDC and other types were associated with an increased risk of relapse (19.1%, 26.7% and 38.2% respectively). Many factors were risk predictors of relapse for TNBC and IDC, while only positive lymph node was for AMC. For MC tumors, adjunctive chemotherapy decreased the risk of relapse in lymph node positive subgroup (36.8% and 66.7%), while not significant in lymph node negative one (8.1% and 10.0%). CONCLUSION: The classification based on histologic and IHC findings may be a significant improvement in predicting outcome in TNBC. The different chemotherapy response in subgroups may contribute to guiding the treatment of TNBC.

A retrospective study of breast cancer subtypes: the risk of relapse and the relations with treatments.

Immunohistochemical markers are often used to classify breast cancer into subtypes that are biologically distinct and behave differently. The aim of this study was to estimate relapse for patients with the major subtypes of breast cancer as classified using immunohistochemical assay and to investigate the patterns of benefit from the therapies over the past years. The study population included primary, operable 2,118 breast cancer patients, all non-specific infiltrative ductal carcinoma, with the median age of 53.2 years. All patients underwent local and/or systemic treatments. The clinicopathological characteristics and clinical outcomes were retrospectively reviewed. The expression of estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin 5/6 were analyzed by immunohistochemistry. All patients were classified into the following categories: luminal A, luminal B, HER2 overexpressing, basal-like, and unclassified subtypes. Ki-67 was detected in luminal A subtype. The median follow-up time was 67.9 months. Luminal A tumors had the lowest rate of relapse (12.7%, P < 0.001), while luminal B, HER2 overexpression, and basal-like subtypes were associated with an increased risk of relapse (15.7, 19.1, 20.9%). Molecular subtypes retained independent prognostic significance (P < 0.001). In luminal A subtype, adjunctive radiotherapy could decrease the risk of relapse (P = 0.005), Ki67 positive was a high-risk factor for relapse (P < 0.001), and adjuvant chemotherapies could reduce the relapse for the patients with risk factors (P < 0.001). Adjuvant hormone therapy was an effective treatment for ER-positive tumors (P < 0.001). Molecular subtypes of breast cancer could robustly identify the risk of recurrence and were significant in therapeutic decision making. The model combined subtype and clinical pathology was a significant improvement. Luminal A tumors might represent two distinct subsets which demonstrated distinct prognosis and therapy response.