Efficacy and Safety Profile of Combining Sorafenib with Chemotherapy in Patients with HER2-Negative Advanced Breast Cancer: A Meta-analysis.

PURPOSE: The aim of the study was to evaluate the efficacy and safety of combining sorafenib with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society for Clinical Oncology abstracts, and European Society for Medical Oncology abstracts were searched. Randomized clinical trials that compared the efficacy and safety of sorafenib plus chemotherapy in patients with HER2-negative advanced breast cancer with placebo plus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression (TTP), duration of response (DOR), overall response rate (ORR), clinical benefits, and adverse effects. The meta-analysis was performed using Review Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random-effect model) was performed to identify the potential cause. The results are expressed as hazard ratios or risk ratios, with their corresponding 95% confidence intervals. RESULTS: The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORR and clinical benefit rates in patients receiving sorafenib combined with chemotherapy compared to those receiving chemotherapy and placebo. OS and DOR were similar in the two groups. Meanwhile, the incidence of some adverse effects, including hand-foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were significantly higher in the sorafenib arm. CONCLUSION: Sorafenib combined with chemotherapy may prolong PFS and TTP. This treatment was associated with manageable toxicities, but frequent dose interruptions and reductions were required.

A clinical study on regional lymphatic chemotherapy using an activated carbon nanoparticle-epirubicin in patients with breast cancer.

The purpose of this study was to understand the short-term therapeutic effects of an activated carbon nanoparticle-epirubicin suspension for regional lymphatic chemotherapy in patients with breast cancer. One hundred and twenty patients with stage I, II, or III primary breast cancer were randomly divided into three groups: the lymphatic chemotherapy group using the activated carbon nanoparticle-epirubicin suspension, the epirubicin control group, and the activated carbon control group. Each group of 40 patients was further divided into two subgroups with the drug injected either 24 or 48 h before surgery. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay was used to determine cancer cell apoptotic indices in metastatic lymph nodes. The epirubicin concentration in the black-stained lymph nodes in the lymphatic chemotherapy treatment group was 4,144.64 ± 2,426.44 ng/g, which is significantly higher than in the epirubicin control group (335.87 ± 212.82 ng/g, P < 0.001). The plasma epirubicin concentrations at 0.5, 1.5, and 24 h postinjection in the regional lymphatic chemotherapy treatment group were significantly lower than in the epirubicin control group (P < 0.001). Tolerable mild pain was observed at the injection area after administration of the epirubicin-activated carbon nanoparticle suspension. No regional necrosis or adverse effects were found. The TUNEL assay demonstrated that there was no significant difference in the apoptotic indices in the metastatic lymph nodes from the three groups. Performing lymphatic chemotherapy by regionally injecting the epirubicin-activated carbon nanoparticle suspension could significantly enhance the drug concentration in the stained lymph nodes and lower the plasma drug concentration. The epirubicin-activated carbon nanoparticle suspension has the ability to release the drug slowly in the lymph nodes and, as a result, can prolong the chemotherapeutic effects.

[Clinical features and prognosis analysis of different breast cancer molecular subtypes].

OBJECTIVE: To investigate the clinical characteristics and prognosis of different breast cancer molecular subtypes. METHODS: Clinicopathological and follow-up data of 1153 cases of operable breast cancer were analyzed retrospectively. Their molecular subtypes were categorized as luminal A, luminal B, Her-2 over-expressing and basal-like subtypes, based on detection of ER, PR, Her-2 expression. The correlation of prognosis of different molecular subtypes with age, tumor size, lymph node status and clinical staging was analyzed. RESULTS: Among the 1153 cases, 791 cases (68.6%) were of luminal A subtype, 50 cases (4.3%) luminal B subtype, 53 cases (4.6%) Her-2(+)subtype, and 259 cases (22.5%) basal-like subtype. There were no statistically significant differences among different molecular subtypes regarding the age, tumor size, lymph node status, and clinical stage. 1006 cases had complete follow-up data and the analysis showed that distant metastasis of Her-2 over-expressing subtype was significantly higher than that in other subtypes (P = 0.005), but the differences of local recurrence rate in different molecular subtypes was not statistically significant (P > 0.05). Kaplan-Meier method was used to analyze the survival prognosis of different molecular subtypes, showing both DFS rate and OS rate of Her-2 over-expressing subtype were the lowest, with a statistically significant difference (Log rank test, P < 0.05). Univariate and multivariate analyses showed that molecular typing and lymph node status were independent prognostic factors affecting both DFS and OS. CONCLUSIONS: Her-2 over-expressing subtype has the worst prognosis. Molecular subtypes may provide important information to predict the prognosis of breast cancer and might be an important basis for individualized treatment of breast cancer in future.