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.
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
Background:American College of Surgeons Oncology Group Z0011 trial showed that axillary lymph node dissection (ALND) had no impact on recurrence and survival in patients with positive sentinel lymph node (SLN) after breast-conserving surgery. However, it is still unknown if the omission of ALND can be applicable to patients treated with mastectomy. The aim of this study wasto evaluate whether ALND could be safely omitted for patients with SLN–positive breast cancer after mastectomy. Methods: From a prospective database of 296 patients with clinically node-negative breast cancer who underwent mastectomy and sentinel lymph node biopsy (SLNB) from March 2006 to December 2016, 81 patients who had positive SLNs were selected. Patient characteristics and prognosis were compared between SLN-positive patients with and without ALND. Patients treated with neoadjuvant chemotherapy were excluded from the analysis. Lymphatic mapping was performed using a combined method of blue dye and radioisotope. Results: The median age of entire patients was 57.0 (range: 32-85) years and the median tumor size was 2.5 (range: 0.6-7.9) cm. Of 81 patients, 23 (28.4%) patients omitted ALND. Patients with SLNB alone were more likely to have smaller SLN involvements (p<0.001): micrometastasis was identified in 13 (56.5%) patients in SLNB-alone group and 9 (15.5%) patients in ALND group. The number of positive SLN was comparable between SLNB-alone (median: 1.0, range: 1-6) and ALND groups (median: 1.0, range: 1-5) (p=0.063). There was no significant difference in characteristics including age, tumor size and tumor subtypes between the two groups. Post-mastectomy radiotherapy was performed in 5 (21.7%) patients with SLNB alone and 16 (27.6%) patients with ALND (p=0.588). The majority of patients with macrometastatic SLN received adjuvant chemotherapy in both groups (83.3% vs. 75.5%, p=0.562). Twenty (87.0%) and 51 (87.9%) patients received adjuvant endocrine therapy in SLNB-alone and ALND group, respectively (p=0.584). After a median follow-up of 54.7 months, no axillary recurrence was observed in both groups and 5-year disease-free survival was not significantly different between the two groups (75.0% vs. 88.8%, p=0.489). Lymphedema was observed significantly more often after ALND than after SLNB (22.4% vs. 4.3%, p=0.045). Conclusions: These data suggested that ALND could be safely omitted in SLN-positive breast cancer patients treated with mastectomy and appropriate systemic therapy. Citation Format: Matsumoto A, Umemoto Y, Jinno H. Validity and safety of omission of axillary lymph node dissection among sentinel lymph node-positive breast cancer patients treated with mastectomy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-30.
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