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

BACKGROUND AND OBJECTIVEThe role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1-T2 tumors and 1-3 positive axillary nodes is still uncertain. This study investigated the value of PMRT for these patients.

METHODSIn the retrospective data of 488 eligible patients, survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a log-rank test and the Cox proportional hazards model, respectively.

RESULTSThe median observation time was 54 months. The 5- and 10-year locoregional recurrence-free survival (LRFS) rates were 90.8% and 86.9%, respectively. The 5- and 10-year disease-free survival (DFS) rates were 82.0% and 74.3%, respectively. The 5- and 10-year overall survival (OS) rates were 90.7% and 82.7%, respectively. For the 412 patients without PMRT, T2 classification, 2-3 positive nodes, and hormone (estrogen and progesterone) receptor-negative were risk factors for locoregional recurrence in the multivariate analysis. On the basis of these 3 risk factors, the group with 2-3 factors had a 10-year LRFS rate of 63.1% compared with 96.1% for the group with 0-1 factors (P < 0.001). For the group with 2-3 risk factors, LRFS and DFS were significantly improved by PMRT, with the 5- and 10-year LRFS rates without PMRT of 82.4% and 63.1%, respectively, and, with PMRT, of 98.1% at both 5 years and 10 years (P = 0.002). The 5- and 10-year DFS rates without PMRT were 72.0% and 57.6%, respectively, and, with PMRT, the 5- and 10-year DFS rates were 89.4% and 81.7%, respectively (P = 0.007). There was no significant difference in the 10-year OS rates between patients with and without PMRT. However, there is the potential benefit of 15.3% (87.1% vs. 71.8%, P = 0.072). Conversely, the group with 0-1 factors of PMRT had no effect on prognosis.

CONCLUSIONSIn patients receiving mastectomy with T1-T2 breast cancer with 1-3 positive nodes, for the group with 2-3 risk factors, PMRT significantly improved LRFS and DFS and has potential benefit in OS.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; radiotherapy ; surgery ; Carcinoma, Lobular ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Radiotherapy, High-Energy ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Risk Factors ; Survival Rate ; Young Adult

Prognostic value of p53 and bcl-2 expression on treatment outcome in breast cancer patients has been extensively evaluated, but the results were inconclusive. We evaluated the prognostic significance of these molecular markers in patients treated with breast conserving surgery and radiotherapy. One hundred patients whose immunostaining of p53 and bcl-2 expression was available among 125 patients who underwent radiotherapy after breast conserving surgery and axillary lymph node dissection were enrolled into this study. Eighty-seven patients also received adjuvant chemotherapy and/or hormonal therapy. Conventional clinicopathologic variables and treatment-related factors were also considered. The 5-yr loco-regional relapse-free and distant metastasis-free survival rates were 91.7% and 90.9%, respectively. On univariate analysis, age, T stage and the absence of bcl-2 & estrogen receptor (ER) expression were associated with loco-regional relapse-free survival. When incorporating these variables into Cox proportional hazard model, only bcl-2(-)/ER(-) phenotype was an adverse prognostic factor (P=0.018). As for the distant metastasis-free survival, age, T stage, and p53 expression were significant on univariate analysis. However, p53 expression was the only prognosticator on multivariate analysis (P=0.009). A bcl-2(-)/ER(-) phenotype and p53 expression are useful molecular markers predicting loco-regional relapse-free and distant metastasis-free survival, respectively, in patients treated with breast conserving surgery and radiotherapy.
Adult ; Aged ; Breast Neoplasms/metabolism/radiotherapy/*surgery ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Humans ; *Mastectomy, Segmental ; Middle Aged ; Multivariate Analysis ; Phenotype ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism ; Receptors, Estrogen/metabolism ; Tumor Suppressor Protein p53/genetics/*metabolism

OBJECTIVETriple-negative [estrogen receptor (ER)-/progesterone receptor (PR)-/HER2-] breast cancer (TNBC) accounts for ∼ 15% of overall breast cancer and associated with a poor prognosis. There is a short of standard adjuvant chemotherapy regimens for TNBC. A number of studies have shown that TNBC might be sensitive to cisplatin and carboplatin on the basis that dysfunction of BRCA1 and its pathway is associated with a specific DNA-repair defect, but data of adjuvant setting about this is limited.

METHODSFrom January 2010 to September 2011, 95 early triple-negative breast cancer patients confirmed by pathology were randomly assigned to receive TP (docetaxel 75 mg/m², carboplatin AUC = 5, day 1, 21 days a cycle for 6 cycles) or EC-T (epirubicin 90 mg/m², cyclophosphamide 600 mg/m², d1, 21 days a cycle for 4 cycles, followed by docetaxel 80 mg/m², d1, 21 days a cycle for 4 cycles) chemotherapy. Adjuvant radiation therapy was given selectively after chemotherapy. Here we report a preliminary safety analysis with the chi-square test.

RESULTSSeventy-six out of the 95 patients had completed the chemotherapy and could be assessed for the safety profiles of the regimens. Thirty-seven of them were in the EC-T group with a median age of 47 years, and 21 out of these 37 patients were premenopausal (56.8%). Another 39 patients came from the TP group with a median age of 46 years, and 22 out of these 39 patients were premenopausal (56.4%). All of the 37 patients in EC-T group completed the planned treatment whereas 2 patients of the 39 cases in TP group did not because of bone marrow suppression. During the treatments, 9 patients had dose adjustment in each group. Adverse events of grade 1/2 were common. Specific incidence of adverse events with grade 3/4 in each group was as follows: alopecia, 29.7% vs. 10.3% (P = 0.033), vomiting 21.6% vs. 7.7% (P = 0.085), leukopenia 54.1% vs.25.6% (P = 0.011) and neutropenia 51.4% vs. 35.9% (P = 0.174). Other grade 3/4 toxicities were rare. All the adverse events (except peripheral neuropathy and pigmentation) recovered within 1 month after the chemotherapy.

CONCLUSIONBoth EC-T and TP regimens as adjuvant chemotherapy are safe and tolerable for the treatment of triple-negative breast cancer patients, while the TP regimen has advantages with less grade III/IV alopecia and leukopenia.

Adult ; Aged ; Alopecia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; radiotherapy ; surgery ; Carboplatin ; administration & dosage ; Carcinoma, Ductal, Breast ; drug therapy ; metabolism ; pathology ; radiotherapy ; surgery ; Chemotherapy, Adjuvant ; Cyclophosphamide ; administration & dosage ; Epirubicin ; administration & dosage ; Female ; Humans ; Leukopenia ; chemically induced ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Premenopause ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Taxoids ; administration & dosage ; Vomiting ; chemically induced

OBJECTIVETo explore different therapies and affecting factors in breast cancer patients ≥ 65 years old.

METHODSTo retrospectively analyze the clinical characteristics, treatments, comorbidity and survival rate of 126 female breast cancer patients over 65 years old who underwent surgical operation in our hospital from January 2009 to December 2010. To compare and analyze the differences in the treatment patterns, and find out the affecting factors.

RESULTSOne hundred and twenty-six cases were included in this retrospective study, and they were divided into two groups according to age: 65-74 years old group (71 cases) and >74 years group (55 cases). Most patients in the two groups received modified radical mastectomy (84.5% and 89.1%); 73.2% and 54.5% of patients received adjuvant chemotherapy in the two groups, respectively. 67.6% and 61.8% of the patients had adjuvant endocrine therapy respectively. 19.7% and 7.3% of the patients received radiotherapy, respectively. Chemotherapy in elderly breast cancer patients was correlated with age, pathological types, progesterone receptor (PR) status and comorbidity. Radiotherapy in elderly breast cancer patients was related to age, surgical patterns, TNM stage and lymph node status. Multivariate analysis showed that age, pathological types, PR expression and comorbidity were independent factors affecting choice of chemotherapy in elderly breast cancer patients (P < 0.05 for all). Age and surgical patterns were independent factors affecting choice of radiotherapy (P < 0.05 for all). The 3-year disease-free survival (DFS) rate and overall survival (OS) rate in these patients were 91.3% and 92.0%, respectively. Furthermore, endocrine therapy was related to 3-year DFS rate (P = 0.038) and age was correlated with 3-year OS rate (P = 0.037) in these elderly patients.

CONCLUSIONSBreast cancer in the elderly patients receive similar surgery and endocrine therapy, but the elderly patients are less likely to have chemotherapy and radiotherapy, due to age, PR expression, pathological types, surgical patterns and comorbidity. Only age contributes to the lower 3-year overall survival rate in >74-year old patients.

Adenocarcinoma, Mucinous ; pathology ; surgery ; therapy ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; pathology ; surgery ; therapy ; Carcinoma, Ductal, Breast ; pathology ; surgery ; therapy ; Carcinoma, Intraductal, Noninfiltrating ; pathology ; surgery ; therapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Humans ; Lymphatic Metastasis ; Mastectomy, Modified Radical ; Mastectomy, Segmental ; Neoadjuvant Therapy ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate

OBJECTIVETo evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy.

METHODSThe clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS).

RESULTS141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS.

CONCLUSIONER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

Adult ; Aged ; Aged, 80 and over ; Anthracyclines ; administration & dosage ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Breast Neoplasms ; metabolism ; pathology ; surgery ; therapy ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; secondary ; surgery ; therapy ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; surgery ; therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Metastasis ; Mastectomy ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Receptor, ErbB-2 ; metabolism ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism ; Retrospective Studies ; Survival Rate ; Taxoids ; administration & dosage ; Trastuzumab ; Young Adult