BTG2 inhibits the proliferation, invasion, and apoptosis of MDA-MB-231 triple-negative breast cancer cells.

The purposes of this study were to investigate the effects of B cell translocation gene 2 (BTG2) on the proliferation, apoptosis, and invasion of triple-negative breast cancer and to provide an experimental basis for the future treatment of human triple-negative breast cancer. A pcDNA3.1-BTG2 eukaryotic expression vector was constructed and transfected into the MDA-MB-231 human triple-negative breast cancer cell line using lipofection. Then, relevant changes in the biological characteristics of the BTG2-expressing cell line were analyzed using MTT (tetrazolium blue), flow cytometry, and Transwell invasion chamber assays. Additionally, the effects of BTG2 expression on cyclin D1, caspase 3, and matrix metalloproteinases 1/2 (MMP-1/-2) expression were analyzed. Cell proliferation was significantly lower in the pcDNA3.1-BTG2-transfected group compared to the empty vector and blank control groups (p<0.05). There was no significant difference between the empty vector and blank control groups. FCM results demonstrated that there were significantly more cells in the G1 phase of the cell cycle and fewer S phase cells in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p<0.05). Additionally, the proportion of cells that migrated across the membrane was significantly lower in the pcDNA3.1-BTG2 group than in the empty vector and blank control groups (p<0.05). Cyclin D1 and MMP-1/-2 expression were significantly lower in MDA-MB-231 cells transfected with pcDNA3.1-BTG2 as compared to the empty vector and blank control groups (p<0.05). Caspase 3 expression was significantly higher in MDA-MB-231 cells from the pcDNA3.1-BTG2 group compared to the empty vector and blank control groups (p<0.05). In conclusion, BTG2 may inhibit MDA-MB-231 proliferation and promote apoptosis. Additionally, BTG2 may also inhibit the invasion of MDA-MB-231 human triple-negative breast cancer cells.

Expression and regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1.

We aimed to evaluate the expression of microRNA-182 (miR-182) in triple-negative breast cancer (TNBC) tissues and the TNBC cell line MDA-MB-231 and to investigate the effects of mirR-182 on the cellular behavior of MDA-MB-231 and the expression of the target gene profilin 1 (PFN1), thus providing new methods and new strategies for the treatment of TNBC. Quantitative real-time PCR (qRT-PCR) was utilized to evaluate the expression of miR-182 in TNBC tissues, relatively normal tissues adjacent to TNBC and the TNBC cell line MDA-MB-231. Forty-eight hours after the MDA-MB-231 cells were transfected with the miR-182 inhibitor, qRT-PCR was utilized to detect the changes in miR-182 expression levels, and an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to determine the effects of miR-182 on cell viability. Flow cytometry was adopted to determine whether miR-182 affects the proliferation rates and apoptosis levels of the MDA-MB-231 cells. The transwell migration assay method was used to investigate the effects of miR-182 on the migration of the MDA-MB-231 cells. A luciferase reporter gene system was applied to validate that PFN1 was the target gene of miR-182. Western blot was used to measure the effects of miR-182 on the PFN1 protein expression levels in the cells. qRT-PCR results showed that compared with the relatively normal tissues adjacent to TNBC, miR-182 expression was significantly increased in the TNBC tissues and the MDA-MB-231 cells (p<0.01). Compared with the control group, MDA-MB-231 cells transfected with the miR-182 inhibitor and incubated for 48 h showed significantly decreased miR-182 expression (p<0.01). The results of an MTT assay showed that inhibition of miR-182 in MDA-MB-231 cells led to significantly reduced cell viability (p<0.05). Flow cytometry analysis indicated that inhibition of miR-182 expression resulted in significantly decreased cell proliferation (p<0.05) and significantly increased levels of apoptosis (p<0.05). The results of a transwell migration assay showed that after inhibited of miR-182 expression, the number of cells passing through the transwell membranes was significantly decreased (p<0.05). The results from a luciferase reporter gene system showed that compared with the control group, the relative luciferase activity of the group transfected with the miR-182 inhibitor was significantly increased (p<0.05). Western blot analysis showed that compared with the control group, PFN1 protein expression levels were significantly increased in the MDA-MB-231 cells transfected with the miR-182 inhibitor and incubated for 48 h (p<0.05). In conclusion, miR-182 is upregulated in TNBC tissues and cells. It promotes the proliferation and invasion of MDA-MB-231 cells and could negatively regulate PFN1 protein expression. Treatment strategies utilizing inhibition of miR-182 expression or overexpression of the PFN1 gene might benefit patients with TNBC.

PCDHB17P/miR-145-3p/MELK/NF-κB Feedback Loop Promotes Metastasis and Angiogenesis of Breast Cancer.

Breast cancer is one of the most common life-threatening cancers, mainly because of its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood. Here, we demonstrated that lncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion, as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decreased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified that MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer. Overall, the results demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK/NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggesting that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.

[Study on diagnostic accuracy of ultrasound-guided core needle breast biopsy].

OBJECTIVE: to evaluate the diagnostic accuracy of ultrasound-guided core needle biopsy of breast tumors. METHODS: six hundred and sixty-seven cases of core needle biopsy of breast encountered during the period from January, 2004 to June, 2007 were retrieved from the archival file and retrospectively reviewed. The core needle biopsy diagnoses were correlated with the histologic findings of the subsequent surgical excision specimens. The discrepancies were further analyzed. RESULTS: three hundred and eighty-two patients had core needle biopsy diagnosis followed by local excision, breast conservation surgery or mastectomy. Two hundred and eighty-one cases were confirmed to have malignancy in the surgical specimens. Review of the corresponding core needle biopsies showed 4 false-negative cases, no false-positive cases, 28 cases with underestimation and 2 cases with overestimation. The false-negative rate was 1.4% (4/281). The rate of underestimation for ductal carcinoma-in-situ was 6/11. The diagnostic accuracy of core needle biopsy was 94.7% (266/281). CONCLUSION: in order to improve the diagnostic accuracy of core needle biopsy of breast tumors, recognition of the limitation of the procedure, application of immunohistochemistry and awareness of potentially rare entities are important.

[Effects of neoadjuvant chemotherapy of docetaxel combined with and epirubicin or pirarubicin on breast cancer: clinical analysis of 160 cases].

OBJECTIVE: To evaluate the effects and toxicity of the neoadjuvant chemotherapy of docetaxel combined with epirubicin or pirarubicin on breast cancer, and to investigate the influencing factors of the response to neoadjuvant chemotherapy. METHODS: 160 patients with stage II/III breast cancer, all females, aged 47 (22-66), were treated with docetaxel plus epirubicin or pirarubicin with 3 weeks as a cycle. Two to six cycles of treatment were given before surgery. The clinical efficacy and toxicity of the treatment were evaluated, and the correlation between the influencing factors and the clinical parameters with treatment response was analyzed. RESULTS: The clinical response rate (RR) was 90% (144/160), the complete response (CR) rate was 26% (41/160), the partial response (PR) rate was 64% (103/160). The stable disease (SD) rate was 8% (13/160). The progress disease (PD) rate was 2% (3/160), the pathologically complete remission (pCR) rate was 7% (11/160), and the tumor-pathological complete response (tpCR) rate was 2% (1.3/160). Univariate analysis showed that the tumor size, clinical stage, triple negative phenotype might be the meaningful parameters influencing the clinical response. The patients with smaller tumor size, low stage tumor, and being triple-negative were more likely to achieve CR (P = 0.0371, 0.0013, and 0.0019 respectively). Age, histological grading, ER/PR ratio, Her-2 status did not significantly influence the early response. Multivariate analysis showed that the disease stage might be the meaningful factors for better response (P = 0.0030). The major toxic reactions of the therapy included neutropenia, alopecia, nausea, and vomiting. CONCLUSION: The combination neoadjuvant chemotherapy with docetaxel and epirubicin or pirarubicin is an effective method to treat breast cancer with tolerable toxicity. The meaningful parameter influencing the early response is clinical stage.

[The clinical study on neoadjuvant chemotherapy with combination of docetaxel and pharmorubicin for locally advanced breast cancer].

OBJECTIVE: To evaluate the clinical efficacy and toxicity of combination neoadjuvant chemotherapy with docetaxel and pharmorubicin in the treatment of locally advanced breast cancer. METHODS: From June 2005 to March 2007, 94 breast cancer patients who have been pathologically confirmed by core needle biopsy were treated with neoadjuvant chemotherapy before operation. Docetaxel 75 mg/m(2) plus pharmorubicin 80 mg/m(2) were administered as intravenous infusion on the first day of each 3-week cycle. Accepted 2 to 4 cycles of the treatment, the patients were underwent surgery after 12 to 16 days. RESULTS: The overall response rate (RR) was 80% (76/94). The complete clinical response rate (CR) was 22% (21/94). The partial response rate (PR) was 58% (55/94). The stable disease (SD) rate was 17% (16/94). The progress disease (PD) rate was 2% (2/94). The pathological complete rate (pCR) was 3% (3/94). The major toxic reactions of the therapy were neutropenia, alopecia, nausea and vomit. 76 patients (80%) suffered with grade 3 to 4 neutropenia. 4 patients suffered with grade 3 to 4 thrombocytopenia. 84 patients suffered with severe alopecia. 90 patients (95%) accepted supportive treatment of G-CSF. Septicemia and death were not occurred in this study. CONCLUSION: The combination neoadjuvant chemotherapy with docetaxel and pharmorubicin is an effective method to treat breast cancer and the toxicities are tolerable.

Status quo and development trend of breast biopsy technology.

Triple assessment is a standard method for assessment of breast diseases, which includes clinical evaluation, radiographic assessment and pathological assessment. Biopsy for breast disease is the gold standard for pathological assessment, including incisional biopsy, excisional biopsy, core needle biopsy, vacuum-assisted biopsy and bite biopsy. With the continuous advancement of diagnostic and treatment technology for breast cancer, collection of diseased tissue has also undergone a gradual transition from traditional open surgery to biopsy. This review summarizes the current situation and development of breast biopsy technology to provide an insight into the latest details such as the safety and reliability as the basis for selection of the most appropriate techniques for specific settings.

Application of immediate breast reconstruction with silicon prosthetic implantation following bilateral mammary gland excision in treatment of young patients with early breast cancer.

OBJECTIVE: To evaluate the application of immediate breast reconstruction (IBR) with silicon prosthetic implantation following bilateral nipple-preserving subcutaneous mammary gland excision in the treatment of young patients with early breast cancer. METHODS: We retrospectively analyzed the clinical data of 21 patients with breast cancer who were performed on IBR following bilateral nipple-preserving subcutaneous mammary gland excision in our hospital from January 2006 to March 2011. RESULTS: The operations were successful in all the 21 patients. Also, the treatment provided a good cosmetic effect. No local recurrence or distant metastasis was found in these 21 patients during the 6-66-month follow-up. CONCLUSIONS: For the young patients with early breast cancer, mammary gland excision on the affected side along with prophylactic excision of the contralateral side, namely IBR following bilateral nipple-preserving subcutaneous mammary gland excision, provides good clinical effectiveness and cosmetological effects.

Intraoperative radiotherapy in patients with breast cancer treated by breast-conserving therapy.

OBJECTIVE: To assess the safety, cosmetic effects, and clinical efficacy of breast-conserving surgery combined with intraoperative radiation therapy for the treatment of Chinese patients with breast cancer. METHODS: Breast-conserving surgery combined with intraoperative radiation therapy was performed in 64 breast cancer patients. The postoperative short-term efficacy, safety, and cosmetic effects were assessed. RESULTS: Of the 64 patients, 1 case (1.6%) had local recurrence one year later, 7 cases (10.9%) had grade I postoperative radiation-induced lung injury, 10 cases (15.6%) had local hardening at the surgical sites, 8 cases (12.5 %) had changes in skin color, and 8 cases (12.5%) had pain at the surgical sites. Excellent or good levels of cosmetic effects were achieved in 95.3% of the patients. CONCLUSIONS: The application of intraoperative radiation therapy with breast-conserving surgery can yield satisfactory short-term curative efficacy, a high level of clinical safety, and good cosmetic effects.

DW-MRI ADC values can predict treatment response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy.

The purpose of this study was to evaluate the importance of diffusion-weighted magnetic resonance imaging (DW-MRI) apparent diffusion coefficient (ADC) values to predict treatment response to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC). Thirty-two patients with LABC underwent 2-4 cylces of NCT (docetaxel and epirubicin). The DW-MRI scans were performed within one week prior to chemotherapy and after the first course of treatment, respectively. Accordingly, tumor volumes, changes in tumor ADC values, and their degree of correlation were analyzed. The overall response (OR) was observed in 62.5% (95% CI, 45.7-79.3%) of patients after 2 cycles of NCT. The clinical complete response (CR) rate and pathological CR (pCR) rate were 15.6 and 9.4%, respectively. The stable disease (SD) rate was 34.4% (11 patients), and progressive disease (PD) was observed in only one patient (3.1%). After the first cycle of NCT, the ADC values in the CR + PR group significantly increased (P < 0.001). The initial ADC values before chemotherapy in the OR group were significantly lower than those in the SD + PD group (P < 0.001). The initial ADC values and the changes in tumor volume after chemotherapy were negatively correlated (r = -0.58, P = 0.02). The lower the initial tumor ADC value was the more obvious the decrease in tumor volume after chemotherapy. The changes in ADC values of tumors after chemotherapy and the changes in tumor volume were positively correlated (r = 0.96, P < 0.001). After chemotherapy, the greater the change in ADC value, the more the tumor volume was reduced. Using the initial ADC values of breast cancer tumors and the early changes in ADC values after NCT, we may be able to predict tumor response to chemotherapy. Tumors with low initial ADC values may be sensitive to chemotherapy; tumors with significantly increasing ADC values early after chemotherapy may be sensitive to chemotherapy.

ER, PgR, HER-2, Ki-67, topoisomerase IIα, and nm23-H1 proteins expression as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer.

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced breast cancer (LABC) One hundred and twelve consecutive patients with clinical stage III LABC who had received NCT with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), Topoisomerase II alpha (Topo-II), and nm23-H1 were detected by immunohistochemistry (IHC). A total of 361 cycles were administered with the median number of three cycles per patient (range, 2-6). The pCR rate was 9.8% (95% CI, 4.3-15.3%). In univariate analysis, poor tumor differentiation, both negative of ER/PgR, negative Topo-II, and positive nm23-H1 were found to be significantly predictive of a pCR. ER/PgR status and nm23-H1 were significant for pCR on multivariate analysis (P = 0.006 and 0.025, respectively). ER/PgR status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with LABC.

Evaluation of ER, PgR, HER-2, Ki-67, cyclin D1, and nm23-H1 as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer.

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with locally advanced breast cancer (LABC). Two hundred and twenty consecutive patients with LABC who had received neoadjuvant chemotherapy (NCT) with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre- and post-neoadjuvant chemotherapy (NCT) treatment expression levels and changes of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). The pCR rate was 9.1% (95% CI, 5.3-12.9%). In univariate analysis, poor tumor differentiation, OR after 2 cycles of NCT, both negative of ER/PgR, negative HER-2, positive cyclin D1, and positive nm23-H1 were found to be significantly predictive of a pCR. Histological grade and ER/PgR status were significant for pCR on multivariate analysis (P = 0.023 and 0.003, respectively). The expression levels of cyclin D1 (median, 8% vs. 9%; P = 0.016) after NCT treatment increased significantly, while the median Ki-67 proliferation index was dramatically decreased after NCT treatment from 35 to 15% (P = 0.036). However, after a Bonferroni adjustment, only the difference of Ki-67 proliferation index was still significant (P = 0.026). Histological grade and ER/PgR status are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in locally advanced breast cancer. Expression of HER-2, Ki-67, cyclin D1, and nm23-H1 were not predictive for pCR.

CK5/6, EGFR, Ki-67, cyclin D1, and nm23-H1 protein expressions as predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients.

The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NCT) in patients with locally advanced triple-negative breast cancers (TNBCs). Forty-one patients (18.6%) among 220 breast cancer patients were identified as TNBCs from March 2006 to 2009 were included in this prospective study. The pre-NCT treatment expression levels of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), CK5/6, epidermal growth factor receptor (EGFR), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). A total of 180 cycles were administered with the median number of four cycles per patient (range, 4-6). The pCR rate was 34.1% (95% CI, 19.6-48.6%). In univariate analysis, early T stage, clinical response after 2 cycles, negative basal-like, negative EGFR, high Ki-67 proliferation index, and positive nm23-H1 were found to be significantly predictive of a pCR (P = 0.010, 0.040, 0.007, 0.001, 0.019, and 0.010, respectively). Basal-like status and nm23-H1 status were significant for pCR on multivariate analysis (P = 0.004 and 0.031, respectively). Basal-like status and nm23-H1 are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with TNBCs.