| Purpose:Approximately 20% of HER2 positive breast cancer developed disease recurrence after adjuvant trastuzumab treatment. A molecular prognostic model that can reliably stratify patients by risk of developing disease recurrence is urgently needed.Patients and Methods:All the patients included were diagnosed as HER2-postive breast cancer and received radical surgery followed by adjuvant trastuzuamb-based treatment. Using miRNA microarrays, we identified nine miRNAs that were differentially expressed between the recurrent and non-recurrent patients. Then, we validated the differential expression of these miRNAs using qRT-PCR in training set (n=101), and built a miRNA-based classifier using the Cox regression model. We further confirmed the prognostic accuracy of this signature in an internal testing set (n=57), and an external independent testing set (n=53).Results:We generated a two-microRNA (miR-4734 and miR-150-5p) prognostic signature that classifies patients into high-risk group and low-risk group, who demonstrated significantly different disease free survival at five years after surgery. The hazard ratio was 5.35 (95%CI 2.13-13.44; p<0.001),3-71(95%CI 1.08-12.74, p=0.025) and 3-43 (95%CI 1.35-8.69; p=0.006) in training set, internal testing set and external testing set, respectively. In the combined analysis of all patients (n=211), the two-miRNA based signature was an independent prognostic factor for prognosis, and had better predictive value than other clinicopathological factors. In combination with TNM stage, the model demonstrated the highest prognostic accuracy (AUC= 0.711,95%CI 0.634-0.787).Conclusion:The two-miRNA-based signature is a reliable prognostic model for disease recurrence in patients with HER2 positive breast cancer who received adjuvant trastuzumab-based treatment, which would be a valuable tool to improve management of this population.Objective to assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.Methods Clinical data on patients diagnosed and treated for mTNBC between 2004 and 2012 at Cancer Hospital, Chinese Academy of Medical Science (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or metastatic settings and patients should have at least one measurable disease.Results Totally,48 patients were included, 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) while 26 patients with NVB plus capecitabine (NX). After 70 months follow-up, in the total population, objective response rate was 20.8%, clinical benefit rate was 43.75%, median progression free survival (PFS) was 4.35 months and median overall survival (OS) was 15.5 months. In addition, ORR was significantly better in NP arm versus NX arm (33.8% vs.7.7% p=0.029) as well as PFS was statistically improved in NP arm than NX arm (5.3m vs 3.0m, p=0.023). Similar trend was observed in OS, although it is not statistical significant (27.7m vs 14.8m, p=0.077). In all, the most frequent adverse events reported was G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%). No significant difference was observed between NP arm and NX arm.Conclusion NVB-based combination chemotherapy demonstrated moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxans with manageable toxicity. NP regimen showed potential superiority over NX regimen, which should be further examined in randomized phase III clinical trial in larger cohort. |
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