Polymorphisms of microRNA genes and their association with breast cancer risk / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between the polymorphisms of microRNA genes and the risk of breast cancer, and to analyze molecular markers which can be used in screening of susceptible population.</p><p><b>METHODS</b>All the individuals included in this case-control study were genetically independent ethnic Han Chinese. The breast cancer patient group consisted of 384 women confirmed by histopathology, and the control group consisted of 192 healthy female individuals. We screened genetic variants in all miRNA genes according to the public database miRBase and NCBI database. A total of twenty-three common single nucleotide polymorphisms in twenty-two miRNAs, which tagged the known common variants with minor allele frequency greater than 0.05 were genotyped. A MassARRAY ® MALDI-TOF system was used for genotyping the candidate SNPs by the method described in the Sequenom Genotyping Protocol. The frequencies of SNPs were compared between cancer cases and controls to identify the SNPs associated with breast cancer susceptibility. Logistic regression analysis was applied to analyze the differences in genotype or allele frequencies of individual SNPs in cancer cases and controls, and to evaluate the correlation between candidate loci and breast cancer risk.</p><p><b>RESULTS</b>The median age of the total group including 384 breast cancer patients and 192 control subjects was 48 years (range, 21-81 years). There were no significant differences in age distribution (P = 0.695) and smoking status (P = 0.193) between the case group and the control group. However, the number of patients with a family history of breast cancer or ovarian cancer in the case group was significantly higher than that in the control group (9.1% vs.1.6%, P < 0.001). The number of the patients with menarche age below 14 years in the case group was significantly higher than that in the control group (53.1% vs.37.5%, P < 0.001). The number of premenopausal patients in the case group was significantly higher than that in the control group (61.2% vs. 50.0%, P = 0.007). There was no significant association between breast cancer risk and the single nucleotide polymorphisms in miRNA genes (P > 0.05).</p><p><b>CONCLUSIONS</b>The genetic polymorphism of miRNA is not obviously associated with breast cancer risk among Chinese women.</p>

Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.</p><p><b>METHODS</b>Clinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).</p><p><b>RESULTS</b>After 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.</p><p><b>CONCLUSIONS</b>NVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.</p>

Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.</p><p><b>METHODS</b>Twenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.</p><p><b>RESULTS</b>With a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).</p><p><b>CONCLUSION</b>Cisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.</p>