[Effects of intestinal flora on the degree of infiltration of tumor-infiltrating lymphocytes in breast cancer].

Objective: To investigate whether the abundance or diversity of intestinal flora in breast cancer (BC) patients effects on the degree of tumor infiltration lymphocytes in breast cancer tissues. Methods: Between March 2017 and October 2017, a total of 80 biopsy-confirmed female patients with BC were enrolled in the present study at the Breast Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China), age distribution ranged from 37 to 74 years, which were divided into three groups based on the infiltration of tumor-infiltrating lymphocytes, as follows: high infiltration of TILs (TIL-H) 25 cases, medium infiltration of TILs (TIL-M) 34 cases and low infiltration of TILs (TIL-L) 21 cases. DNA of the intestinal flora was determined by Illumina sequencing and taxonomy of 16S ribosomal RNA genes. Compare the differences in the abundance or diversity of intestinal flora between these three groups. The relationship between tumor-infiltrating lymphocytes and clinical characteristics was analyzed by χ2 tested, and the relationship with intestinal flora was analyzed by ß diversity. Results: There were 3, 174, 2, 996, and 2, 877 different OUTs in the TIL-H, TIL-M, and TIL-L groups. The ß-diversity distribution was statistically significant (weighted UniFrac, P<0.01; unweighted UniFrac, P<0.01) when comparing the three groups (TIL-H vs. TIL-M vs. TIL-L), the differences between TIL-L and TIL-H groups were greatest. Conclusions: The infiltration level of tumor-infiltrating lymphocytes in breast cancer patients was closely related to the diversity of intestinal flora.

[The Breast Cancer Cohort Study in Chinese Women: the methodology of population-based cohort and baseline characteristics].

Objective: Breast cancer has been the first cancer among women with the incidence increasing gradually. In September 2016, the Breast Cancer Cohort Study in Chinese Women (BCCS-CW) was initiated, aiming to establish a standardized and sharable breast cancer-specific cohort by integrating the existing cohort resource and improving the quality of follow-up. The BCCS-CW may provide a research basis and platform for the precision prevention and treatment of breast cancer in etiology identification, prevention, early diagnosis, treatment, and prognosis prediction. Methods: We conducted a population-based perspective cohort by questionnaire interview, anthropometry, biological specimens, breast ultrasound and mammography. The cohort was followed by using regional health surveillance and ad hoc survey. Results: Finally, BCCS-CW included 112 118 women, in which 55 419 women completed the standardized investigation and blood specimens were collected from 54 304 women. The mean age of participants was 51.7 years old, 62.7% were overweight or obese, and 48.9% were menopausal. Conclusion: The BCCS-CW will provide population-based cohort resource and research platform for the precise prevention and treatment of breast cancer in Chinese women.

[Clinical analysis of 382 immediately breast reconstruction after mastectomy in Beijing City, Tianjin City and Hebei Province from 2012 to 2016].

Objective: To summarize the status of immediate breast reconstruction (IBR) after mastectomy in Beijing City, Tianjin City and Hebei Province. Methods: A retrospective analysis was made on the data of 382 cases with breast cancer who were treated and followed up successfully with immediate breast reconstruction after mastectomy from January 2012 to December 2016 in Beijing City, Tianjin City and Hebei Province. Clinic data of the followed-up 382 cases (all female, age (38.5±4.2) years (range: 24 to 70 years)), including general information, tumor information, sugery methods, and treatments after surgery were collected. The survival status, metastasis,complications and prognosis were followed up. Cosmetic effcet was evalated by Harris method, and life quality by Functional Assessment of Cancer Therapy-Breast scale (FACT-B). χ(2) test was used to compare the difference between year 2012 and year 2013 to 2016. Bonferroni method was used to correct the inspection level, which was 0.05/10=0.005. The trend of IBR rate (ratio of IBR to modified radical mastectomy) from 2013 to 2016 was analyzed by trend χ(2) test. Results: There was 46 cases in stage 0, 152 cases in stage Ⅰ, 165 cases in stage Ⅱ, 19 cases in stage Ⅲ. Twenty-five cases was treated by neoadjuvant chemotherapy, 231 by chemotherapy and 35 by radiotherapy. The proportion of implant reconstruction was 48.7% (186/382), more than expanded of 21.5% (82/382), with latissimus dorsi of 12.0% (46/382), TRAM of 8.9% (34/382), DIEP of 2.1% (8/382), and latissimus plus implant of 6.8% (26/382). According to the Harris standard, the excellent and good rate of the cosmetic effect of the reconstructed breast was 93.7%. The score of FACT-B was 108.20±16.9 (range: 67 to 144) 1 year postoperatively. Compared with 2012, the IBR rate was significant increased, till 2015, the IBR rate was 153/10 000 cases (χ(2)=47.028, P=0.000). Conclusions: There is a significant increase on IBR rate in Beijing City, Tianjin City and Hebei province by year. Most of cases received IBR is stage Ⅰ to Ⅱ. Implant reconstruction is the main reconstructive method. Postoperative cosmetic effects and quality of life are both meet patients' demon.

Molecular mechanisms of long chain non-coding RNA CTBP1-AS in regulation of invasion and migration of breast cancer cells.

This study aimed to investigate the role of long-chain non-coding RNA CTBP1-AS in breast cancer progression and cell invasion as well as migration. Clinical data of breast cancer patients (N = 155) in our hospital was collected for further analysis. qRT-PCR was used to detect LncRNA CTBP1-AS expression levels in human normal breast epithelial cell (MCF-10A) and breast cancer cells (MCF-7, BT- 549, MDA-MB-231 and MDA-MB-435). LncRNA CTBP1-AS knock-down and overexpressed lentivirus vectors were constructed to transfect breast cancer cells. Colony formation assay was employed to detect cell proliferative abilities. Flow cytometry was performed to detect cell apoptosis ratio. Wound healing scratch assay was used to detect cell migration, and Transwell matrigel assay was used to detect cell invasion. Bioinformatics analysis was performed to predict the downstream targets of LncRNA CTBP1-AS, which were further validated by dual-luciferase reporter gene system. The results showed that LncRNA CTBP1-AS was aberrantly overexpressed in breast cancer tissues and breast cancer cells compared to the control group. Moreover, the expression levels of LncRNA CTBP1-AS were positively related with tumor size, histological grade and the expression levels of Ki-67 and Her2. Further analysis showed that LncRNA CTBP1-AS expression levels negatively correlated with patient survival time and clinical prognosis. Of note, overexpressed LncRNA CTBP1-AS promoted breast cancer cell proliferation and invasion as well as migration, and decreased cell apoptosis ratio. Bioinformatics analysis and dual-luciferase reporter gene system results validated that microRNA-940 was the downstream target of LncRNA CTBP1-AS. Interestingly, overexpressed microRNA-940 abrogated the effects of LncRNA CTBP1-AS on cell proliferation, apoptosis, and invasion. In conclusion, overexpressed LncRNA CTBP1- AS promoted breast cancer cell proliferation, invasion as well as migration, inhibited cell apoptosis and accelerated breast cancer development by sponging microRNA-940.

[A multicenter, randomized, controlled, phase â £ clinical study of PEG-rhG-CSF for preventing chemotherapy induced neutropenia in patients with breast cancer].

Objective: To explore the efficacy and safety of polyethylene glycal recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patiens with breast cancer. Methods: There were two parts in the present phase Ⅳ clinical study. One was a randomized, controlled clinical study. Patients in this study received PEG-rhG-CSF or rhG-CSF in the first cycle and followed with both PEG-rhG-CSF in the rest of 3 cycles. The other one was a single arm study. Patients who developed Ⅲ/Ⅳ grade neutropenia in the screening cycle received PEG-rhG-CSF in the rest of 3 cycles chemotherapy. Results: In the first cycle of randomized, controlled study, the incidence of Ⅳ grade neutropenia are 31.48% and 35.58% respectively in PEG-rhG-CSF and rhG-CSF group, with no statistically significant differences (P=0.527 6). The duration of Ⅳ grade neutropenia respectively are 2.22±1.58 and 3.00±1.59 days, with a statistically significant difference (P=0.016 6). In the single arm study, the incidence of Ⅳ grade neutropenia was 57.76% in screening cycle. And the incidence decreased to 16.35%, 10%, and 8.57% in the followed 3 cycle after the use of PEG-rhG-CSF. The incidence of adverse effects was 5.06%, and the major adverse effect was bone pain which with an incidence of 2.8%. Conclusion: The fixed 6mg dose of PEG-rhG-CSF can effectively prevent neutropenia in patients with breast cancer in multicycle chemotherapy and it has a low incidence of adverse events and mild adverse reaction.

[Study of bioequiavailability of paclitaxel for Injection (Albumin Bound) and abraxane and the efficacy of extension treatments in patients with metastatic breast cancer].

Objective: To compare the bioequiavailability of paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane in the patients with metastatic breast cancer, and to investigate the safety and efficacy in the extension treatments of PAB. Methods: This study was random, two cycles, self-crossover control study in the bioequiavailability stage. PAB was the investigational drug T and Abraxane was the reference drug R. Patients were randomly assigned to two cycles therapy of either R→T or T→R(260 mg/m(2)/21d). Non-PD patients entered in the extension treatments of the investigational drug PAB(260 mg/m(2)/21d) until the disease progression or the intolerance toxicity. Results: From Mar 1, 2016 to May 24, 2016, we enrolled 40 patients. The blood concentration-time curve and the parameters of pharmacokinetics indicated the two drugs were the bioequivalent drug products in the initial two cycles crossover-therapy.The incidence of adverse drug reactions were 89.7% vs 97.4% in investigational drug vs reference drug and grade 3/4 toxicities were 20.5% vs 21.1%(P=1.000). Patients received a median of 7 treatment cycles(range 1-23) and a median of 260mg/m(2) actual drug dose (range 220-260 mg/m(2)). Seven patients (17.5%) had dose reductions because of toxicities (260 mg/m(2) reduce to 220 mg/m(2)). Twenty-two patients (55%) discontinued treatment prematurely because of toxicity.Overall response rates (ORR) were 40% (95% CI, 24.8%-55.2%). For patients who received PAB as first-line vs non-first-line therapy, the ORR were 43.8% vs 25%. For patients who taxane-naïve vs taxane-pretreated, the ORR were 45.5% vs 37.9%. Median PFS was 49 weeks(95% CI, 30weeks-NA). Conclusion: The paclitaxel for injection (albumin bound) (PAB) and reference listed drug abraxane are the bioequivalent drug products.The toxicity and efficacy of the PAB are similar with abraxane.The more therapy chances for Chinese patients will come by the research and development of domestic drugs.

[Correlation between extranodal invasion in axillary lymph node metastasis and prognosis of breast cancer patients].

Objective: To investigate the significance of extranodal extension of axillary lymph nodes (ALN-ENE) metastases in post-operative primary invasive breast carcinoma of non-specific type. Methods: Six hundred and thirty-eight invasive breast cancer cases confirmed by postoperative pathological examination were collected from January 2006 to December 2008. The relationship of lymph node metastases and ALN-ENE with other lymph node parameters and patient outcome was analyzed. Results: Among 638 cases, 263 (41.2%) showed axillary lymph node metastases. ALN-ENE was present in 91 cases (36.4%). The rate of ALN-ENE increased with pT stage and tumor size. Five-year recurrence-free survival rate (RFS) and 5-year overall survival rate (OS) was 86.6% and 91.2% respectively for ALN-ENE positive group, and both were lower than ALN-ENE negative group (P<0.01). One hundred and forty-nine patients with 1 to 3 positive lymph nodes had a 5-year RFS of 91.9%, and 5-year OS of 92.3%, less than ALN-ENE negative group (P<0.01). Univariate analysis showed ALN-ENE positively correlated with lymph node metastasis. Multivariate analysis suggested that ENE was associated with increased recurrence risk and shortened recurrence-free and overall survival, especially in patients with 1 to 3 positive lymph nodes; and it was an independent prognostic factor (P<0.01). Conclusions: The number of lymph nodes metastases is an important predictor of survival in breast cancer patients. ALN-ENE is an independent risk indicator for recurrence and overall survival. For patients with 1 to 3 metastatic axillary lymph nodes, ALN-ENE could alter the patient's clinical pathologic staging, and therefore it is an independent prognostic factor.

[Circulating tumor cells in patients with breast tumors were detected by a novel device: a multicenter, clinical trial in China].

Objective: Circulating tumor cells (CTC) have become an important part of liquid biopsy, which have underwent a process from simple counting to molecular typing and genotyping. To this end, we used Cellcollector to verify the effectiveness and safety of CTC detection in patients with breast tumor, and to conduct the following analysis. Methods: One hundred and ninety patients who received treatment in six leading Chinese cancer centers were involved from April to August in 2016. Among which, 127 patients were diagnosed as metastatic breast cancer, and the other 63 patients as benign breast tumors. Results: In metastatic breast cancer group, 74.8%(95/127) were CTC positive. While in benign tumor group, they were all CTC negative patients. The area under the Receiver Operating Characteristic curve were 0.832(95%CI: 0.784-0.879). The sensitivity of Cellcollector was 74.8%, specificity was 100% (Youden index 0.748). A total of 117 patients in MBC groups received a second detection of Cellcollector after 3-4 weeks, among which 44.4% (52/117) were CTC positive patients. The incidence of adverse events and severe adverse events in MBC was 66.9%(85/127) and 39.8% (53/127). Furthermore, we used Cellcollector to perform the HER2 testing and gene sequencing. Conclusions:In vivo isolation of CTCs overcomes blood volume limitations compared to other approaches. The further application of molecular typing and gene typing might help to implement CTC-based "liquid biopsies" into clinical decision making.