Loss of microRNA-145 expression is involved in the development and prognosis of breast cancer complicated by type 2 diabetes mellitus.

OBJECTIVE: To explore the relationships of the expression of miR-145 to the clinicopathological characteristics and prognosis of patients with breast cancer complicated by type 2 diabetes mellitus (T2DM). METHODS: A total of 257 female patients with breast cancer were enrolled for our experiment, including 140 patients with simple breast cancer (control group) and 117 patients with breast cancer complicated by T2DM (observation group). Patients were treated with modified radical mastectomy supplemented with radiotherapy, chemotherapy and endocrine therapy. qRT-PCR was used for the detection of miR-145 expression in patients of both groups. Follow-up lasted 13-60 months. RESULTS: The relative expression of miR-145 in the observation group was significantly lower than that in the control group (p<0.05). The expression of miR-145 in patients with breast cancer complicated by T2DM was related to the history of diabetes, tumor node metastasis (TNM) stage, tumor size, lymph node metastasis (LNM), estrogen receptor (ER) status, and HER2 (all p<0.05). The median disease-free survival (DFS) was significantly longer and the 5-year DFS rate significantly higher in the high-expression group than in the low-expression group. History of diabetes, TNM stage, tumor size, LNM, ER status, and HER2 were risk factors for patients with breast cancer complicated by T2DM (all p<0.05). CONCLUSIONS: Loss of miR-145 expression is related to the development of breast cancer complicated by T2DM, and low miR-145 expression might be an adverse prognostic factor in patients with this disease.

Lymphangiogenic characteristics of triple negativity in node-negative breast cancer.

PURPOSE: Triple-negativity breast cancer (TNBC), being negative for the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, represents a subgroup of breast cancer with a poor clinical outcome. The aim of the study was to determine whether TNBC is associated with lymphangiogenesis in node-negative breast carcinomas. METHODS: The authors investigated the clinicopathologic characteristics, lymphatic vessel density (LVD), and expression of 2 lymphangiogenic factors, vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D), in 21 lymph node-negative TNBCs and 70 lymph node-negative non-TNBCs. RESULTS: TNBC correlated with younger age (below 35 year) and higher histological grade. It also correlated with a higher intratumoral and peritumoral LVD, positive lymphatic invasion, and positive VEGF-C and VEGF-D expression. CONCLUSIONS: For the first time, this study indicated a link between triple-negativity breast cancer and lymphangiogenesis. Lymphangiogenesis might help explain the special malignant phonotype of breast cancer, and lymphangiogenesis inhibitors might be a novel choice for triple-negativity breast cancer patients.

Paclitaxel-doxorubicin sequence is more effective in breast cancer cells with heat shock protein 27 overexpression.

BACKGROUND: Cancer cells with overexpression of heat shock protein 27 (HSP27) are resistant to chemotherapeutic drug doxorubicin (Dox). Paclitaxel (Pacl) was reported to suppress HSP27 expression in ovarian and uterine cancer cells. The purposes of this study were to investigate whether Pacl inhibits the expression of HSP27 in breast cancer cells, whether Pacl can sensitize breast cancer cells with HSP27 overexpression to Dox, and to define a more effective schedule for the combination of Dox with Pacl. METHODS: The HSP27 high-expressing human breast cancer cell lines, MCF-7 and MDA-MB-435, and the HSP27 low-expressing cell line, MDA-MB-231, were used in this study. The level of HSP27, topoisomerase (Topo) IIalpha and beta expression were assessed by Western blotting. The cytotoxic activities of Dox, Pacl and combination of these two drugs were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometric assays. RESULTS: Pacl (0.1 micromol/L) inhibited HSP27 expression by approximately 2-fold in MCF-7 and MDA-MB-435 cells, while up-regulating the level of topo IIalpha and beta. In contrast, expression of HSP27 in MDA-MB-231 did not change significantly following Pacl treatment. There were synergistic effects in both treatment sequences (Pacl-Dox and Dox-Pacl) when Pacl was combined with Dox. Compared with those treated with the Dox-Pacl sequence, the Pacl-Dox sequence had a stronger effect in cancer cells with HSP27 overexpression, as MCF-7 and MDA-MB-435 treated with the Pacl-Dox sequence had lower viabilities and a higher apoptotic rate. CONCLUSIONS: Paclitaxel significantly decreases the level of HSP27 in breast cancer cells overexpressing HSP27. In combination therapies, the Pacl-Dox sequence is more effective in clearing breast cancer cells with high HSP27 expression compared with the Dox-Pacl sequence.