Patients with human epidermal growth factor receptor 2(HER2)-positive breast cancer are prone to develop brain metastases.Inefficient drug delivery due to the blood-brain barrier/blood-tumor barrier is a major dilemma in the systemic treatment of brain metastases.Therefore,patients with HER2-positive breast cancer brain metastasis usually have few treatment options and poor prognosis.In traditional opinions,it is difficult for macromolecule drugs to cross the blood-brain barrier,but with the in-depth understanding of the properties of the blood-brain barrier/blood-tumor barrier,this view has gradually changed,especially when several clinical studies have validated the efficacy of new antibody-drug conjugates(ADC)in patients with brain metastasis in the recent years.These findings have provided more treatment options for HER2-positive breast cancer patients with brain metastasis.This review introduces the mechanism of systemic treatment drugs and sorts out the current important advances in systemic treatment for HER2-positive breast cancer patients with brain metastases,hoping to provide some reference for the clinical practice of treatment for HER2-positive breast cancer brain metastases in China.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Purpose: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. Materials and Methods: One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. Results: Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. Conclusion Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

Objective:To investigate the effects of ligamen remnant preservation on knee joint function and proprioception recovery in patients with anterior cruciate ligament (ACL) injuries during ACL reconstruction under arthroscope.Methods:The clinical data of 266 patients with ACL injuries,who were treated in the 174th hospital of PLA from January 2010 to March 2016,were retrospectively analyzed.All the patients underwent ACL reconstruction under arthroscopy,among them,163 patients with remnant preservation were chosen as remnant preservation group;103 patients with completely clearing remnant preservation in the operation,as non remnant preservation group.All the patients were followed up for more than 12 months,and the knee function and proprioception recovery of the two groups were evaluated.Results:There were no significant differences in the knee ipsilateral Lysholm score,international knee documentation committee knee assessment scale (IKDC) score,passive activity detection threshold,passive angle regeneration test results between the two groups before operation,9 and 12 months after operation (P＞0.05).The Lysholm scores and IKDC scores of the two groups at each time point were significantly higher than those before operation,the passive activity detection threshold and passive angle regeneration test results were significantly lower than those before operation (P＜0.05).The Lysholm scores and IKDC scores in the remnant preservation group 3 and 6 months after operation were higher than those in the non remnant preservation group,the passive activity detection threshold and the passive angle regenerated test results were lower than the non remnant preservation group,the difference was statistically significant (P＜0.05).Conclusion:Remnant preservation in the ACL reconstruction under arthroscopy can accelerate the recovery of knee joint function and proprioception,and satisfactory clinical results are achieved,which is worth popularizing.

Objective To fully assess the status of cancer chemotherapy quality of secondary and tertiary hospitals in Shanghai City in order to improve the quality control system of cancer chemotherapy.Method According to the supervision plan of Shanghai Cancer Chemotherapy Quality Control Center,all of the 103 secondary and tertiary hospitals in Shanghai City which administrated chemotherapy to cancer patients have been inspected in 2015.SPSS13.0 was used for data aggregation and analysis.Result The cancer chemotherapy quality was significantly different between the secondary and tertiary hospitals,as well as between the oncoiogy and non-oncology departments,the main problems were as follow.:the informed consent content was incomplete (33.04％);pathological diagnosis was incomplete or missing (15.50％);tumor stage was not standardized or no staging (56.27％);the chemotherapy purposes (42.44％) and the chemotherapy indications (37.47％) and contraindications (12.21％) were incomplete or missing;the evaluation of chemotherapy efficacy was incomplete or not evaluated (24.10％);the mid-term assessment was incomplete or not evaluated (27.72％);admission history (16.28％) and records of the chemotherapy day (32.04％) were incomplete or missing.Conclusion The quality of medical records of cancer chem0therapy in Shanghai City is significantly related to hospital level and specialty.The hospital authorities should learn the quality control standards based on their own problems.

Objective To compare the efficacy of single-tunnel single-bundle and double-bundle reconstruction in patients with anterior cruciate ligament reconstruction.Methods A total of 64 patients with anterior cruciate ligament rupture in our hospital were randomly divided into single-bundle group with 32 cases and double-bundle group with 32 cases, given single-tunnel single-bundle anterior cruciate ligament reconstruction, and single-tunnel double-bundle anterior cruciate ligament reconstructions.The IKDC, Tegner, Lysholm and KT-2000 scores were compared in two groups preoperation and at 12 months after operation.Results Thee were no significant difference in sex, age, injured site and injured time in the two groups(P>0.05).The IKDC, Tegner and Lysholm scores after operation were higher than operation before, and the KT-2000 scores was lower than operation before in two groups, and the differences were statistically significant(P<0.05).But there were no significant differences in IKDC, Tegner, Lysholm and KT-2000 scores between two groups before and after treatment(P>0.05).Conclusion The subjective and objective function scores of two groups showed no significant difference.But single-tunnel double-bundle for anterior cruciate ligament reconstruction is characterized by simplicity, firmly fixation and effectively restoration of knee stability.

Objective To compare the efficacy of single-tunnel single-bundle and double-bundle reconstruction in patients with anterior cruciate ligament reconstruction.Methods A total of 64 patients with anterior cruciate ligament rupture in our hospital were randomly divided into single-bundle group with 32 cases and double-bundle group with 32 cases, given single-tunnel single-bundle anterior cruciate ligament reconstruction, and single-tunnel double-bundle anterior cruciate ligament reconstructions.The IKDC, Tegner, Lysholm and KT-2000 scores were compared in two groups preoperation and at 12 months after operation.Results Thee were no significant difference in sex, age, injured site and injured time in the two groups(P>0.05).The IKDC, Tegner and Lysholm scores after operation were higher than operation before, and the KT-2000 scores was lower than operation before in two groups, and the differences were statistically significant(P<0.05).But there were no significant differences in IKDC, Tegner, Lysholm and KT-2000 scores between two groups before and after treatment(P>0.05).Conclusion The subjective and objective function scores of two groups showed no significant difference.But single-tunnel double-bundle for anterior cruciate ligament reconstruction is characterized by simplicity, firmly fixation and effectively restoration of knee stability.

Background and purpose:The third generation of aromatase inhibitors (AI) in postmenopausal hormone receptor-positive patients is the routine treatments in endocrine therapy. The 500 mg fulvestrant showed clini-cal beneifts in patients with previous AI treatment. This study aimed to access the effcacy and safety of 500 mg fulves-trant in estrogen receptor (ER) positive postmenopausal patients who had previous AI treatments with locally advanced and metastatic breast cancer.Methods:This study retrospectively analyzed the clinical data from 188 post-AI ER positive and (or) progesterone receptor (PR)-positive locally advanced and metastatic breast cancer patients treated with 500 mg fulvestrant in Fudan University Shanghai Cancer Center from Jul. 2011 to Dec. 2015. Primary end point was progression-free survival (PFS). Secondary end points were objective response rate (ORR), clinical beneift rate (CBR) and safety proifle.Results:After the median follow-up of 11.3 months, median PFS was 5.9 months (95%CI: 4.2-7.5), CBR was 40.0% and ORR was 3.4%. COX proportional hazards regression analysis indicated that PFS was correlated with the number of metastatic sites (HR=1.92, 95% CI: 1.2-2.9,P =0.002) and previous lines of chemotherapy (HR=1.52, 95%CI:1.0-2.1,P=0.022). Six patients stopped the treatment for intolerable adverse events.Conclusion:The treatment of 500 mg fulvestrant has a favorable effcacy and safety in treatment of post-AI ER positive postmenopausal patientswith metastatic breast cancer.

Antineoplastic Agents, Hormonal ; therapeutic use ; Breast Neoplasms ; chemistry ; drug therapy ; Female ; Humans

Background and purpose:Gemcitabine-based chemotherapy has been shown to have signiifcant activity and favourable safety in metastatic breast cancer patients, but the effectiveness is limited due to drug resistance. MicroRNAs are a family of small non-coding RNA molecules, acting as oncogenes or tumor suppressors. Although various mechanisms of chemoresistance have been uncovered, the aberrant microRNA expression and its relationship with drug resistance of breast cancer are still unclear. This study explored the potential role and underlying mechanism of microRNA-21 in gemcitabine resistant breast cancer. Methods:MDA-MB-231 cells were continuously exposed to the increasing concentrations of gemcitabine to induce drug resistance to gemcitabine, which was 10 times more resis-tant. Then multiple methods were used including real-time PCR (RT-PCR), CCK-8, Western blot, transfection, wound healing and Transwell assay to observe the effect of microRNA-21 on epithelial-mesenchymal transition (EMT) and chemosensitivity. Results:The expression of microRNA-21 was up-regulated in gemcitabine resistant breast cancer cell line and inversely correlated with gemcitabine sensitivity. Manipulation of microRNA-21 status could change microR-NA-21 level, and could result in corresponding changes in EMT status and drug sensitivity. Conclusion:MicroRNA-21 induces gemcitabine resistance possibly via EMT process in breast cancer.