Objective: To investigate the effect of cinobufacini on proliferation, celly cycle distribution, invasion capability of MDA-MB-231 breast cancer cell line in vitro and possible mechanism. Methods: The effect of cinobufacini on cell growth was measured by CCK-8 reagent kit. Cell cycle distribution was determined by flow cytometry. The invasion capability in vitro was detected by Transwell chamber assay. The mRNA expressions of cell cycle related factors (cyclin) and p21 were tested by RT-PCR. Results: Cinobufacini inhibited proliferation of MDA-MB-231 cells. The half inhibition concentration (IC50) was 0.31 mg/mL. The inhibitory effect was timE-dependent (P<0.05). Cinobufacini significantly decreased invasion capability of MDA-MB-231 cells in vitro compared with control group (P<0.05). Cinobufacini induced S-phase arrest of MDA-MB-231 cells in a concentration-dependent manner (P<0.000 1). Cinobufacini down-regulated the expression levels of cyclin A1, cyclin D1, and cyclin E1, while up-regulated that of p21 in MDA-MB-231 cell line. However, there was no marked change in the expression of cyclin B1. Conclusion: Cinobufacini inhibits cell proliferation and influences the cell cycle distribution in vitro by regulating the expression of cyclin A1, cyclin D1, cyclin E1 and p21 in breast can-cer cells.

OBJECTIVETo evaluate the available surgical treatment modalities so as to explore the optimal strategy of managing early breast cancer.

METHODSThe clinical data of 2173 consecutive early-stage breast cancer patients treated by surgery treatments were retrospectively reviewed in order to clarify the indications and contraindications of different modalities. Therapeutic outcome of different surgical treatment modes were compared in terms of recurrence-free survival ( RFS) , disease-free survival ( DFS) , overall survival (OS). The cosmetic results of breast conservation and reconstruction were also evaluated .

RESULTSThe median age of these patients was 51 years ranging from 18 to 91. Of 2173 patients, 547 had stage 0- I lesions and 1626 stage II , and 1155 (53. 2% ) premenopausal. The proportion of patients who received radical surgery, breast conservation and reconstruction after mastectomy was 83. 6% (1817/2173), 10. 5% (229/2173) and 2. 5% (55/2173) , respectively. Younger and premenopausal patients prefer conservative and reconstructive surgeries, which are reasonable for stage 0-I and non-invasive breast cancer patients. Conservative surgery was not suitable for Paget's disease of breast (P = 0. 004) , mastectomy followed by reconstruction in this type of cancer was up to 38. 5%. The recurrence and metastasis rate of conservation or mastectomy were similar with a comparable 3-year RFS of 97. 4% and 95. 4% , respectively; there were also no significant differences in RFS(P =0. 2435) , DFS( P =0. 1395) and OS(P =0. 9406) after having been followed for 3 to 64 months. Similarly, immediate reconstruction did not show any negative effects with only 1 recurrence and 1 metastasis. Aesthetic outcomes were assessed as excellent or good in 90. 0% of breast conservation surgery, and the acceptability of reconstruction was 94. 5%.

CONCLUSIONBreast conserving surgery not only has comparable survival as mastectomy, but also has better cosmetic outcomes. Immediate breast reconstruction can be a suitable option without compromising survival. It is very important in the management for early breast cancer by selecting the most suitable surgery mode for every individual patient not only to cure her disease but also to satisfy the patient psychologically. Conservation should be preferred prior to reconstruction whenever possible.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; pathology ; surgery ; Carcinoma, Ductal, Breast ; pathology ; surgery ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Mastectomy ; methods ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Paget's Disease, Mammary ; pathology ; surgery ; Reconstructive Surgical Procedures ; Retrospective Studies

Objective To explore the influencing factors for postoperative adjuvant chemotherapy effects in elderly patients with breast cancer. Methods Five hundred and ninety female patients aged 65 years or older with invasive breast cancer were treated in our hospital, and the influencing factors for postoperative adjuvant chemotherapy effects were analyzed by chi-square test and logistic regression. Results Two hundred and thirty-one (39.2%) patients received postoperative adjuvant chemotherapy. The results showed that diabetes, age, patterns of operation and pathological characteristics of tumor had significant influences on postoperative adjuvant chemotherapy effects (χ2=4.49,88. 27,23.49 and 9.40, all P<0.05). Logistic regression analysis showed that age, tumor size, lymph node status(pN) and estrogen receptor (ER) status were related to postoperative adjuvant chemotherapy effects(χ2=68.857,15. 284,43. 540 and 7.009 ,all P<0.01). Forty-four patients (66.7%) with pN(+)/ER(-) received adjuvant chemotherapy. Conclusions Age, tumor size, lymph node status and ER status were independent predictive factors for postoperative adjuvant chemotherapy effects in elderly patients with breast cancer.

Background and purpose:Rabs are members of Ras-related small GTPase superfamily. Rab27A is a unique member in the Rab family and has specific implications in human genetic diseases. We studied the potential role of Rab27A in proliferation, distribution of cell cycle, apoptosis and invasion of breast cancer cells and its mechanism(s). Methods:The eukaryotic expression vector containing Rab27A open reading frame (ORF) pcDNA3.1(+) - Rab27A was constructed and transfected into MDA-MB-231 breast cancer cells. Then we detected the changes in terms of cell growth, cell cycle distribution, apoptosis and in vitro invasion capability before and after transfection. We also applied RT-PCR to investigate the molecular basis.Results:① The expression of Rab27A was increased as invasive and metastatic ability increased in four human breast cancer cell lines. ② Overexpression of Rab27A can promote breast cancer cells to grow faster, increase the proportion of S phase cells, avoid apoptosis and invade in vitro. ③ Rab27A transfectants constitutively enhanced the expression of Cyclin D1, MMP-7 and MMP-9 in MDA-MB-231 cell lines, on the contrary, that of p16 were down-regulated constitutively. Reduced Rab27A expression by RNAi down-regulated the expression of Cyclin D1, MMP-7 and MMP-9, and up-regulated p16 expression.Conclusions:Rab27A can stimulate breast cancer cells to proliferate, increase the proportion of cells in S phase,avoid apoptosis and invade in vitro by regulating the expression of Cyclin D1, MMP-7, MMP-9 and p16.

OBJECTIVETo study the effects of aromatase on breast cancer proliferation and invasive ability, so as to detect the relationship between in situ estrogen levels and molecular biological characteristics of breast cancer.

METHODSBy immunohistochemistry staining, the expression of aromatase, matrix metalloproteinases 2 (MMP2) and matrix metalloproteinases (MMP 9) in the primary breast cancers were detected, the associations between aromatase and MMPs as well as clinical-pathological factors were analyzed.

RESULTSThe positive rates of aromatase were 25.0% (+) and 29.9% (++). Aromatase status was associated with MMP2, MMP9 and co-expression of MMP2 and MMP9 (P < 0.05), but not associated with tumor size, ER/PR status, menopausal status and tumor grade (P > 0.05). In the postmenopausal patients there was a relationship between aromatase and tumor size (P < 0.05), but not in the premenopausal patients (P > 0.05); there was a relationship between aromatase and co-expression of MMP2/MMP9 in the patients with ER and/or PR positive (P < 0.05), but not in the patients with ER and PR negative (P > 0.05).

CONCLUSIONSIn the breast cancer in situ estrogen produced by tumor aromatase may promote the cancer cells proliferation and invasiveness and maybe through ER pathway especially in the postmenopausal patients.

Adult ; Aged ; Aromatase ; metabolism ; Breast Neoplasms ; enzymology ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

OBJECTIVETo summarize the clinical experience of trastuzumab treatment in neoadjuvant, adjuvant, metastatic setting of Chinese patients with Her-2 positive breast cancer and evaluate the efficacy of trastuzumab in combination with chemotherapy.

METHODSFrom January 2004 to December 2008, 141 outpatients with breast cancer treated with trastuzumab were investigated retrospectively. The follow-up time ranged from 3 to 319 months. The disease free survival time (DFS) of metastatic setting was calculated. The overall survival time (OS), time to treatment failure (TTF) and clinical response rate (CRR, including complete response, partial response and stable disease) of adjuvant, first-line, second-line therapy were analyzed statistically.

RESULTSIn the neoadjuvant regimen, paclitaxel plus carboplatin in combination with trastuzumab accounted for 66.7%, which achieved pathological complete response in 10 of 16 patients. In the adjuvant regimen, anthracycline or anthracycline followed by taxane accounted for 53.9%. The median DFS of 57 cases with metastatic diseases was 17 months. The CRR of first-line trastuzumab use in metastatic setting was 84.5%, compared with 44.4% of second-line use. The median TTF of first-line treatment was 24 months compared with 5 months of second-line treatment. Statistically significant differences were observed.

CONCLUSIONThe regimen of paclitaxel plus carboplatin in combination with trastuzumab deserves wide clinical use. In metastatic setting, first-line treatment of trastuzumab plus chemotherapy can achieve a higher response rate than second-line treatment. Continued trastuzumab therapy combined with different chemotherapy treatment after disease progression may obtain additive clinical advantage.

Adult ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal, Humanized ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Bridged-Ring Compounds ; administration & dosage ; Carboplatin ; administration & dosage ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Paclitaxel ; administration & dosage ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Treatment Failure

OBJECTIVETo identify predictive markers of the long-term outcome for neo-adjuvant chemotherapy (NC) in locally advanced breast cancer (LABC) treated with intravenous vinorelbine (V) and epirubicin (E) combination regimen.

METHODSOne hundred and nineteen patients with LABC were treated from September 2001 to May 2006. All patients were diagnosed as invasive breast cancer by 14G core needle biopsy and treated with three cycles of VE regimen before the operation. The patients were subjected to surgery and subsequently were given other three cycles of VE or cyclophosphamide+epirubicin+fluorouracil (CEF) regimen according to the clinical responses. Local-regional radiotherapy was applied to all patients after the chemotherapy and followed by hormone-therapy according to hormone receptor status. The impact of clinical, pathological, and immunohistochemical features on disease free survival (DFS) and overall survival (OS) was evaluated.

RESULTSAll patients were evaluable for responses: clinical complete response was documented in 27 patients (22.7%), 78 patients (65.5%) obtained partial clinical response. The pathological complete response was found in 22 cases (18.5%). Of the patients, 115 cases (96.6%) were followed-up for a median time of 63.4 months (range, 9-76 months), the 5-year DFS rate and OS rate was 58.7% and 71.3%, respectively. On multivariate analysis, high pre-Ki-67 (P=0.012) and post-Ki-67 expression (P=0.045), no pathological complete response after NC (P=0.034) were associated with the higher risk of disease relapse; high pre-Ki-67 (P=0.017) and post-Ki-67 expression (P=0.001), negative pre-ER (P=0.002) and no pathological complete response after NC (P=0.034) were associated with a shorter survival.

CONCLUSIONPathological response in primary tumor, pre-Ki-67 and post-Ki-67 expression, pre-ER expression are important predictors of long-term outcome for LABC patients with three cycles of VE regimen before operation.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Epirubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Middle Aged ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Vinblastine ; administration & dosage ; analogs & derivatives

BACKGROUNDSeroma formation is one of the most common complications after breast cancer surgery. Various risk factors have been evaluated for their associations with the development of seromas in Western populations. However, similar data are not available in Chinese series. Therefore, we sought to investigate the potential risk factors for Chinese breast cancer patients.

METHODSA prospective study of female breast cancer patients undergoing surgery was carried out in Cancer Hospital of Fudan University, Shanghai, China. Univariate analyses were performed by chi-square test or Student's t test or Mann-Whitney test and multivariate analyses by stepwise Logistic regression. The logistic model included age (years), total serum protein concentration (g/L), drainage volume on postoperative day 3 (POD 3; ml) and time to daily drainage volume not more than 30 ml (TTV30; days).

RESULTSA total of 158 patients with breast cancer were studied. The mean age at diagnosis was (52.14 ± 10.77) years (range 25 - 92). During the follow-up period, 24 (15.2%) patients developed seromas. Calculated as continuous variables in the stepwise Logistic regression, age (OR = 1.090, 95%CI 1.028 - 1.155, P = 0.004), total serum protein concentration (OR = 0.886, 95%CI 0.791 - 0.992, P = 0.036), drainage volume on POD3 (OR = 1.013, 95%CI 1.002 - 1.023, P = 0.017) and TTV30 (OR = 1.273, 95%CI 1.039 - 1.561, P = 0.020) were independent risk factors for seroma formation. Additionally, significant difference in daily drainage volume was substantiated in the analysis by seroma formation (P = 0.034) rather than by type of surgery (P = 0.713).

CONCLUSIONSAlthough the pathogenesis of seroma remains controversial, such risk factors as age, nutritional status, drainage volume on POD3 and TTV30 should be considered for prediction and prevention of seroma formation in Chinese breast cancer patients.

Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; Breast Neoplasms ; surgery ; Female ; Humans ; Middle Aged ; Postoperative Complications ; Prospective Studies ; Risk Factors ; Seroma ; etiology

OBJECTIVETo study the "hot spot" of BRCA1/2 gene mutations in Chinese mainland breast cancer population.

METHODSThe known BRCA1/2 gene mutations in author's previous studies were reanalyzed by denaturing high performance liquid chromatography and DNA sequencing method in 177 patients with early onset breast cancer or affected relatives and 426 sporadic breast cancer patients from four breast cancer centers in China.

RESULTSThree cases were found with BRCA1 5589del8 mutation out of 247 hereditary-predisposing breast cancer patients (70 patients in previous study and 177 patients in current study) and 2 cases with BRCA1 5589del8 mutation out of 426 sporadic breast cancer patients. They had similar even same haplotype.

CONCLUSIONBRCA1 5589del8 mutation is likely to be the "founder mutation" in Chinese population, but it should be confirmed by further studies.

Adult ; Asian Continental Ancestry Group ; genetics ; BRCA1 Protein ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; Chromatography, High Pressure Liquid ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Mutation

OBJECTIVETo investigate the expression of ER alpha in chemically induced, ER alpha-negative human breast cancer MDA-MB-435 cells and its restoration of the responsiveness to endocrine therapy.

METHODSMDA-MB-435 cells were treated with HDAC inhibitor trichostatin A(TSA)and DNMT1 inhibitor 5-AZA-CdR (AZA). The mRNA level of ER alpha, PR and PS2 in treated MDA-MB-435 cells was detected by RT-PCR. The WST-8 (water-soluble tetrazolium salt-8) method was used to analyze the proliferation rate of the cells. Xenograft in female nude mice was used to further explore the change of proliferation rate of treated MDA-MB-435 cells in vivo.

RESULTSAfter treatment with AZA and TSA, mRNA expression of ER alpha, PR and pS2 was up-regulated in MDA-MB-435 cells. The mRNA level of ER alpha was the hightest when MDA-MB-435 cells were treated with 2.5 micromol/L AZA and 100 ng/ml TSA. The treated MDA-MB-435 cells showed different proliferation rate in various media containing different concentration of estrodial. The MDA-MB-435 cells showed down-regulated proliferation rate after treatment with the combination of 2.5 micromol/L AZA and 100 ng/ml TSA, and 4-OH tamoxifen could suppress the growth rate of the induced MD-MBA-435 cells but not the untreated cells. The treated MDA-MB-435 cells showed slower proliferation rate than that of untreated cells in vivo (P <0. 01), and the proliferation rate of the treated MDA-MB-435 cells became lower when the nude mice were deprived of estrogen by castration (P <0. 01).

CONCLUSIONAfter treatment with TSA and AZA, ER alpha-negative MDA-MB-435 cells can express functional ER alpha and regain responsiveness to estrogen both in vitro and in vivo. HDAC inhibitor and DNMT1 inhibitor may play an important role in restoration of sensitivity of ER alpha-negative breast cancers to endocrine therapy.

Animals ; Azacitidine ; analogs & derivatives ; pharmacology ; Breast Neoplasms ; genetics ; pathology ; prevention & control ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Modification Methylases ; antagonists & inhibitors ; Enzyme Inhibitors ; pharmacology ; Estrogen Receptor alpha ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Histone Deacetylase Inhibitors ; Humans ; Hydroxamic Acids ; pharmacology ; Mammary Neoplasms, Experimental ; genetics ; pathology ; prevention & control ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Ovariectomy ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Progesterone ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Trefoil Factor-1 ; Tumor Suppressor Proteins ; genetics ; Xenograft Model Antitumor Assays