OBJECTIVETo examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis.

METHODSThe osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay.

RESULTSCompared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1 (P<0.05 or P<0.01).

CONCLUSIONBrucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

Animals ; Bone Neoplasms ; metabolism ; prevention & control ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Female ; Humans ; Jagged-1 Protein ; metabolism ; Macrophages ; drug effects ; physiology ; Mice ; Osteoclasts ; drug effects ; physiology ; Receptor, Notch1 ; metabolism ; Signal Transduction ; drug effects ; Strychnine ; analogs & derivatives ; pharmacology ; therapeutic use

Cytokines are believed to be involved in a "vicious circle" of progressive interactions in bone metastasis. Iguratimod is a novel anti-rheumatic drug which is reported to have the capability of anti-cytokines. In this study, a rat model was constructed to investigate the effect of iguratimod on bone metastasis and it was found that iguratimod alleviated cancer-induced bone destruction. To further explore whether an anti-tumor activity of iguratimod contributes to the effect of bone resorption suppression, two human breast cancer cell lines MDA-MB-231 and MCF-7 were studied. The effect of iguratimod on tumor proliferation was detected by CCK-8 assay and flow cytometry. The effects of iguratimod on migration and invasion of cancer cells were determined by wound-healing and Transwell assays. Results showed that high dose (30 μg/mL) iguratimod slightly suppressed the proliferation of cancer cells but failed to inhibit their migration and invasion capacity. Interestingly, iguratimod decreased the transcription level of IL-6 in MDA-MB-231 cells in a concentration-dependent manner. Moreover, iguratimod partially impaired NF-κB signaling by suppressing the phosphorylation of NF-κB p65 subunit. Our findings indicated that iguratimod may alleviate bone destruction by partially decreasing the expression of IL-6 in an NF-κB-dependent manner, while it has little effect on the tumor proliferation and invasion.
Animals ; Apoptosis ; drug effects ; Bone Neoplasms ; complications ; drug therapy ; pathology ; secondary ; Bone Resorption ; complications ; drug therapy ; pathology ; Breast Neoplasms ; complications ; drug therapy ; genetics ; pathology ; Carcinogenesis ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Chromones ; administration & dosage ; Female ; Humans ; Interleukin-6 ; biosynthesis ; genetics ; MCF-7 Cells ; Neoplasm Invasiveness ; genetics ; pathology ; Rats ; Sulfonamides ; administration & dosage ; Transcription Factor RelA ; biosynthesis ; genetics

OBJECTIVETo explore the clinical features, management approach and treatment outcomes for adenoid cystic carcinoma (ACC) of the breast.

METHODSThe clinicopathological data of 25 patients with breasts ACC treated in our hospital from years 1990 to 2012 were retrospectively reviewed and their prognosis was analyzed.

RESULTSThe median age of these 25 patients was 53 years (ranged from 31 to 81 years). With the exception of one male case, all patients were female including 17 cases of postmenopausal women. The most frequent presenting symptom is breast lumps, most (48.0%) were in the upper outer quadrant and areola area of the breast. Core needle biopsy was performed in five patients. The specimen finding were adenoids in three and invasive carcinoma in two cases. Axillary lymph node dissection was performed in 23 patients. Only two patients had histologically positive lymph nodes (3 of 14 and 2 of 20). Expression of ER and PR in 14 cases was detected by immunohistochemistry, showing one PR-positive and three ER-positive cases. The median follow-up of the 25 cases was 118 months (ranged from 12 to 244 months). Two patients died of lung metastases at 3 and 10 years after the surgery, respectively.

CONCLUSIONSDue to the complexity of the histology of ACC, adequate sampling of specimens is essential for accurate diagnosis. ACC of the breast is a rare disease with a relatively good prognosis. The low incidence of axillary lymph node metastasis suggests that axillary node dissection is not recommended as a routine procedure. Breast ACC are often with negative ER and PR expression, and the value of adjuvant therapy needs to be further investigated.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Axilla ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Breast Neoplasms, Male ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Carcinoma, Adenoid Cystic ; drug therapy ; metabolism ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide ; therapeutic use ; Female ; Fluorouracil ; therapeutic use ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mastectomy ; methods ; Methotrexate ; therapeutic use ; Middle Aged ; Postmenopause ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies

OBJECTIVETo investigate the safety and efficacy of trastuzumab administered concurrently with anthracycline-containing adjuvant regimen for breast cancer.

METHODSIt is a prospective, randomized and controlled trial. Participants were randomized to receive trastuzumab administered concurrently or sequentially with anthracycline-containing adjuvant regimen. The primary endpoint was cardiac safety. The second endpoints were disease-free survival (DFS) and overall survival (OS).

RESULTSOne hundred and nine breast cancer patients were enrolled and randomized in this trial. Fifty-five participants received trastuzumab administered concurrently with anthracycline-containing adjuvant regimen and 54 patients received trastuzumab administered sequentially with anthracycline. The primary cardiac event was asymptomatic decrease in the left ventricular ejection fraction (LVEF). There was no significant difference between concurrent and sequential groups in cardiac event rates (9.1% vs13.0%, P = 0.556), neither of LVEF values at basline or at 3, 6, 9 and 12 months during trastuzumab treatment (P > 0.05). Four patients (7.3%) in the concurrent group suffered local recurrences or distant metastases, and 6 participants (11.1%) in the sequential group had distant metastases. There was no significant difference between the two groups in DFS (P = 0.724). There was no death in both groups.

CONCLUSIONSTrastuzumab administered concurrently with anthracycline is a safe adjuvant regimen for breast cancer and does not increase cardiac events. Further research is needed to determine the efficacy of this treatment regimen.

Adult ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal, Humanized ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Prospective Studies ; Stroke Volume ; Trastuzumab

No abstract available.
Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use ; Breast Neoplasms/*pathology ; Female ; Humans ; Liver Cirrhosis/etiology/*radiography ; Liver Neoplasms/drug therapy/*radiography/secondary ; Middle Aged ; Neoplasm Staging ; Tomography, X-Ray Computed

No abstract available.
Adenocarcinoma/*diagnosis/radiography/secondary ; Adult ; Antineoplastic Agents/therapeutic use ; Breast Neoplasms/*diagnosis/drug therapy/pathology ; Carrier Proteins/metabolism ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Endoscopy, Digestive System ; Female ; Glycoproteins/metabolism ; Humans ; Mastectomy, Modified Radical ; Positron-Emission Tomography and Computed Tomography ; Stomach Neoplasms/*diagnosis/radiography/secondary ; Taxoids/therapeutic use ; Tomography, X-Ray Computed

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments.
Animals ; Bone Neoplasms ; drug therapy ; metabolism ; radiotherapy ; secondary ; surgery ; Breast Neoplasms ; metabolism ; pathology ; Disease Models, Animal ; Drug Delivery Systems ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Prostatic Neoplasms ; metabolism ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

OBJECTIVETo analyze the clinicopathological features and prognostic factors of breast cancer patients with inguinal lymph node metastases.

METHODSSeventeen breast cancer patients with inguinal lymph node metastases were treated from January 1999 to December 2010 in our cancer center. All of the patients had a history of breast cancer without other primary cancer. Their clinicopathological characteristics and prognostic factors were surveyed.

RESULTSThe frequency of breast cancer cases with inguinal lymph node metastaseis consisted of 0.11% of the total number of breast cancer patients in the same period. Two patients (11.8%) had inguinal lymph node metastasis only, and multi-site metastases were observed in the remaining 15 (88.2%) patients. The number of ER- and/or PR-positive and negative were 10 (58.8%) and 7 (41.2%) cases, respectively, and among the 13 cases who underwent HER-2 test, the number of HER-2-positive was 4 (30.8%). For the 16 patients who underwent surgery, 9 patients were detected with metastatic axillary lymph nodes equal or greater than 4. All of the 17 patients were treated with chemotherapy.The median follow-up time was 156 months. The 5-year overall survival rate was 49.9%. Univariate analysis revealed that metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, disease stage as III/IV at diagnosis and the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis ≤ 36 months were predictors of shorter PFS (P < 0.05). Metastatic axillary lymph nodes ≥ 4, ER- and(or) PR-negative, adjuvant chemotherapy ≤ 6 cycles, primary recurrence as multiple distant metastases, the period from diagnosis of breast cancer to the occurrence of inguinal lymph nodes metastasis ≤ 36 months and pleural effusion were predictors of shorter OS (P < 0.05). Multivariate analysis revealed that the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis was an independent prognostic factor concerning PFS (P < 0.05).

CONCLUSIONSThe prognostic factors of breast cancer patients with inguinal lymph node metastases include the number of metastatic axillary lymph nodes, ER and(or) PR status, the cycles of adjuvant chemotherapy, type of primary recurrence, the period from diagnosis of breast cancer to the occurrence of inguinal lymph node metastasis and pleural effusion. Regular and complete physical examination after surgery as well as prompt intensive treatment for high-risk patients may have positive significance in the treatment of such type of patients. However, a type of more reasonable and individualized treatment is warranted in future studies.

Adult ; Aged ; Axilla ; Bone Neoplasms ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; secondary ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Groin ; Humans ; Liver Neoplasms ; secondary ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Middle Aged ; Neoplasm Recurrence, Local ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Survival Rate

OBJECTIVETo evaluate the clinical characteristics and prognosis of adrenal metastasis from breast cancer, and to explore methods to improve prognosis.

METHODSThirty-four breast cancer patients with adrenal metastasis were diagnosed and treated in our hospital from Jan. 1999 to Dec. 2010. SPSS 17.0 was used for survival analysis.

RESULTSDuring the Jan. 1999 to Dec. 2010 period, 13 595 patients with breast cancer were treated in our hospital. Among them, 34 cases had adrenal metastasis from breast cancer, with an incidence of 0.25%. The median time to progression (TTP) and overall survival of the 34 patients was 6.2 months (95%CI 3.1-9.3 months) and 21.4 months (95%CI 0-44.0 months), respectively. Eleven patients (34.4%) achieved partial response among 32 patients who received chemotherapy, and 10 (31.2%) achieved stable disease. Patients who achieved best response of PR or SD were superior in TTP and OS than patients with disease progression after chemotherapy (TTP: 18.1 months vs. 2.3 months, P < 0.001; OS: 35.2 months vs. 10.3 months, P = 0.003). Patients who received 1st or 2nd line chemotherapy were superior in TTP than patients who received over 2nd line chemotherapy (TTP: 15.7 months vs. 4.2 months, P = 0.005).

CONCLUSIONSThe incidence of adrenal metastasis from breast cancer is low. Chemotherapy-based systemic therapy should be recommended to improve the prognosis for these patients.

Adrenal Gland Neoplasms ; drug therapy ; secondary ; surgery ; Adrenalectomy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; surgery ; Disease Progression ; Female ; Humans ; Middle Aged ; Remission Induction ; Retrospective Studies ; Survival Rate

OBJECTIVEPure epithelial breast metaplastic carcinoma is a rare and highly malignant tumor. In this study, our purpose was to analyze the clinical features, treatment method and prognostic factors, so to explore the approach for early diagnosis and appropriate treatment of this cancer.

METHODSClinical data of 22 patients with histopathologically confirmed pure epithelial breast metaplastic carcinoma and treated at Tianjin Cancer Hospital from 1974 to 2008, were reviewed retrospectively. Survival rate was calculated by life tables. Kaplan-Meier unvariate analysis and Log-rank test were used to compare the survival rates. Multivariate factors for survival were analyzed by Cox proportional hazards regression model.

RESULTSThe median age of the 22 cases of pure epithelial breast metaplastic carcinoma was 52.5 years. Among them 20 cases went to see a doctor for painless mass, and two cases shown as skin inflammation. Clarifying a diagnosis was difficult before operation so that its diagnosis mainly depended on postoperative histopathologic examination. Twelve cases had axillary lymph node metastasis, 7 cases distant metastasis, and the lung was the most common metastatic organ. The 5-year survival rate was 55.6%, with a median follow-up of 46 months. It was found by Kaplan-Meier unvariate analysis that the age (P = 0.044), number of positive axillary lymph nodes (P = 0.011) and therapeutic schedule (P = 0,003) significantly influenced the outcome of the patients, but tumor size (P = 0.194) was not. Cox multivariate analysis results showed that number of positive axillary lymph nodes was independent prognostic factor for pure epithelial breast metaplastic carcinoma (P = 0.038).

CONCLUSIONSPure epithelial breast metaplastic carcinoma is seldom seen. It is easy to cause distant metastasis and has a poor prognosis. ER, PR and HER-2 expressions in most samples are negative. The more axillary lymph nodes have metastasis, the poorer is the prognosis. A reasonable and comprehensive treatment can improve the prognosis obviously.

Adult ; Aged ; Aged, 80 and over ; Axilla ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Adenosquamous ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; radiotherapy ; secondary ; surgery ; Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Mastectomy, Radical ; methods ; Middle Aged ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate