PurposeMicroRNAs (miRNAs) play an essential role in breast malignant tumor development and progression. The development of clinically validated biomarkers for primary breast cancer (BC) has remained an insurmountable task despite other advances in the field of cancer molecular biology. The objective of this study is to investigate the differential expression of miRNAs and the potential of circulating microRNAs as novel primary breast cancer biomarkers.MethodsOur analyses were performed on 48 tissue and 100 serum samples of patients with primary BC and a set of 20 control samples of healthy women, respectively. The relative expression of ten candidate miRNAs (miR-106b, miR-125b, miR-17, miR-185, miR-21, miR-558, miR-625, miR-665, miR-92a, and miR-93) from the results of four bioinformatics approaches and literature curation was measured by real-time quantitative reverse transcription PCR (qRT-PCR).ResultsThe level of miR-92a was significantly lower, while miR-21 was higher, as previous reports, in tissue and serum samples of BC than that of healthy controls (p < 0.001). Logistic regression and receiver operating characteristic curve analyses revealed the significant and independent value (p < 0.001) of the miR-92a and miR-21 expression quantification in serums. Moreover, the comparison with the clinicopathologic data of the BC patients showed that decreased levels of miR-92a and increased levels of miR-21 were associated with tumor size and a positive lymph node status (p < 0.001).ConclusionsThese findings suggest that many miRNAs expressions are altered in BC, whose expression profiling may provide a useful clue for the pathophysiological research. Circulating miR-92a has potential use as novel breast cancer biomarker, which is comparable to miR-21.

ObjectivePD-1 inhibitors have improved efficacy in many cancers. There are currently no reports of the use of PD-1 inhibitors, such as nivolumab, for metastatic biliary tract cancer (mBTC). This study reviewed the efficacy and safety of nivolumab for mBTC with the aim of exploring ways to improve efficacy and survival.MethodsThirty patients with mBTC were voluntarily treated with nivolumab at the PLA General Hospital. Nivolumab 3 mg/kg was administered. Progression-free survival (PFS) and overall survival were evaluated by Kaplan–Meier and univariate and multivariate analyses were carried out for clinical characteristics. Objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (AEs) were also evaluated.ResultsThe median treatment cycle is four cycles. One case was complete response, 5 cases partial response, 12 cases stable, and 12 cases progression. ORR was 20%, DCR was 60%, and PFS was 3.1 months (95% CI: 2.13–4.06). The AEs of nivolumab monotherapy were fatigue (three cases), fever (two cases), hypothyroidism (one case), skin reaction (one case), and liver injury (one case). Nivolumab combined with chemotherapy related grade 1–2 hematologic toxicity were leukopenia (five cases) and thrombocytopenia (two cases), and grade 3–4 were leukopenia (three cases). Non-hematologic toxicity grade 1–2 were nausea and vomiting (four cases), fatigue (four cases), fever (three cases), peripheral neurotoxicity (three cases), and hypothyroidism (one case). Univariate analysis showed that PFS of nivolumab combined with chemotherapy was statistically significant compared with that of nivolumab monotherapy (4.1 vs 2.3 months, P=0.031). Programmed death-ligand 1 (PD-L1) expression positively has no relationship with better PFS in contrast with PD-L1 negatively (3.6 vs 3.0 months P>0.05). Multivariate analysis show nivolumab combined with chemotherapy was only the independent factor for longer PFS (HR: 0.432, P<0.05).ConclusionThe safety of nivolumab in mBTC is controllable. Further selection of superior populations is needed to improve the efficacy of nivolumab in mBTC.

No definitive treatment strategy has been established for patients with metastatic colorectal cancer (mCRC) who experienced progression after three or more lines of chemotherapy. A total of 36 mCRC patients were enrolled in this retrospective study who received apatinib therapy under non-clinical trial setting after progression in People’s liberation army general Hospital from March 2015 and August 2017. Progression free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR) and treatment-related adverse events (AEs) were reviewed and evaluated. Five patients achieved partial response (PR), and 25 achieved stable disease (SD), and 6 achieved progression disease (PD), illustrating a DCR of 83.3% and an ORR of 13.9%. Median PFS was 3.82 m and median OS was not reached. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 adverse event incidence of 27.8%. The most common grade 3/4 adverse events were hypertension (n = 4, 11.1%), liver function damage (n = 3, 8.3%) and hand–foot syndrome (n = 2, 5.6%). No drug-related death occurred. Apatinib therapy provides a reasonable option with an acceptable safety profile for Chinese mCRC patients failed to prior chemotherapy.

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