Patients diagnosed preoperatively with ductal carcinoma (DCIS) breast cancer have the potential to develop invasive ductal carcinoma (IDC). The present study investigated the usefulness of exosome-encapsulated microRNA-223-3p (miR-223-3p) as a biomarker for detecting IDC in patients initially diagnosed with DCIS by biopsy. The potential association between miR-223-3p and clinicopathological characteristics was examined in patients with breast cancer. Exosomes of 185 patients with breast cancer were separated from plasma by ultracentrifugation. Initially a microRNA (miRNA) microarray was examined to reveal the invasion specific miRNAs using exosomes collected from 6 patients with breast cancer, including 3 DCIS patients, 3 IDC patients and 3 healthy controls. In the miR microarray analysis the miR-223-3p levels of IDC patients demonstrated the highest fold-change compared with those in the DCIS patients and healthy controls. The potential of miR-223-3p for cell proliferation and cell invasion were examined using MCF7 cells transfected with the miR-223-3p gene. MCF7 cells transfected with the miR-223-3p gene significantly promoted cell proliferation and cell invasive ability (P<0.05). The plasma exosomal miR-223-3p levels of the other 179 patients with breast cancer and 20 healthy controls were measured using TaqMan miR assays. The exosomal miR-223-3p levels of the patients with breast cancer were significantly increased compared with the healthy controls (P<0.01). A statistically significant association was observed between the exosomal miR-223-3p levels and histological type, pT stage, pN stage, pathological stage, lymphatic invasion and nuclear grade (P<0.05). The exosomal miR-223-3p levels of IDC patients (stage I) and upstaged IDC patients (stage I) were significantly higher compared with the DCIS patients (P<0.05). These results suggest that exosomal miR-223-3p may be a useful preoperative biomarker to identify the invasive lesions of DCIS patients diagnosed by biopsy. In addition, plasma exosome-encapsulated miR-223-3p level was significantly associated with the malignancy of breast cancer.
San Antonio Breast Cancer Symposium 2016). The model with 4 factors, including the histologic type (invasive ductal or lobular), the expression level of PgR (Allred score 7,8 or < 6) and Ki67 (< 24 or > 24), and the presence of lymphovascular invasion, showed that 92% of patients with high PgR positive and Ki67 < 24 could be classified as low-RS with an AUC of 0.843 (95%CI: 0.790-0.896). The aim of this study was to validate our prediction model with external patient data. Methods: A validation set of clinicopathological data from 77 patients who had primary invasive carcinoma surgically resected and underwent OncotypeDxV R was obtained from Showa University, school of medicine, Tokyo, Japan. Results: According to the distribution of 4 factors between two cohorts, there was a significant difference in Ki67 level (<0.01) but not in histologic type, the expression level of PgR, and lymphovascular invasion. The prediction model of the validation cohort had still high enough discriminatory ability having an AUC of 0.705 (95%CI: 0.584-0.827). Conclusions: Regardless of the inconsistency of Ki67 level between institutes, our model could provide useful information to predict low-RS in hormone receptor-positive invasive breast cancer patients. This model would be helpful to select patients who had better apply OncotypeDXV R . Legal entity responsible for the study: Yasue Tsuchida Funding: None Disclosure: All authors have declared no conflicts of interest.
peripheral neuropathy was assessed by the investigator and confirmed by the other medical oncologists according to CTCAE version 4.0. Result: Of 84 patients who received paclitaxel, 25 received neoadjuvant, and 59 received adjuvant chemotherapy. Median age of the patients was 50 years (range 27-74). 38 of the patients had peripheral neuropathy over grade 2, and 46 of them had under grade 1. The serum samples before treatment of those patients were randomly divided to training set and test set (2:1). 3 formulas with combination of four miRNAs were found to be able to predict peripheral neuropathy (PNmiR sets). PNmiR sets had a sensitivity, specificity and accuracy over 75% in the test cohort. It should be noted that one of the four miRNAs, which constructs two of the three formulas, represents the drug-transporter protein P-glycoprotein, potentially promoting paclitaxel resistance. Conclusion: The combination of four miRNAs (PNmiR set) measured from serum can be used to predict peripheral neuropathy by paclitaxel-contained chemotherapy. One of the potential miRNAs suggests the relation with metabolism of paclitaxel.O2 À 8 À 5 Prognostic value of subtype changes after neoadjuvant chemotherapy in primary breast cancer
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