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Objective: To evaluate the feasibility of using a multigene signature to tailor individualised adjuvant therapy for patients with operable triple negative breast cancer., Design: Randomised, multicentre, open label, phase 3 trial., Setting: 7 cancer centres in China between 3 January 2016 and 17 July 2023., Participants: Female patients aged 18-70 years with early triple negative breast cancer after definitive surgery., Interventions: After risk stratification using the integrated signature, patients at high risk were randomised (1:1) to receive an intensive adjuvant treatment comprising four cycles of docetaxel, epirubicin, and cyclophosphamide followed by four cycles of gemcitabine and cisplatin (arm A; n=166) or a standard treatment of four cycles of epirubicin and cyclophosphamide followed by four cycles of docetaxel (arm B; n=170). Patients at low risk received the same adjuvant chemotherapy as arm B (arm C; n=168)., Main Outcome Measures: The primary endpoint was disease-free survival in the intention-to-treat analysis for arm A versus arm B. Secondary endpoints included disease-free survival for arm C versus arm B, recurrence-free survival, overall survival, and safety., Results: Among the 504 enrolled patients, 498 received study treatment. At a median follow-up of 45.1 months, the three year disease-free survival rate was 90.9% for patients in arm A and 80.6% for patients in arm B (hazard ratio 0.51, 95% confidence interval (CI) 0.28 to 0.95; P=0.03). The three year recurrence-free survival rate was 92.6% in arm A and 83.2% in arm B (hazard ratio 0.50, 95% CI 0.25 to 0.98; P=0.04). The three year overall survival rate was 98.2% in arm A and 91.3% in arm B (hazard ratio 0.58, 95% CI 0.22 to 1.54; P=0.27). The rates of disease-free survival (three year disease-free survival 90.1% v 80.6%; hazard ratio 0.57, 95% CI 0.33 to 0.98; P=0.04), recurrence-free survival (three year recurrence-free survival 94.5% v 83.2%; 0.42, 0.22 to 0.81; P=0.007), and overall survival (three year overall survival 100% v 91.3%; 0.14, 0.03 to 0.61; P=0.002) were significantly higher in patients in arm C than in those in arm B with the same chemotherapy regimen. The incidence of grade 3-4 treatment related adverse events were 64% (105/163), 51% (86/169), and 54% (90/166) for arms A, B, and C, respectively. No treatment related deaths occurred., Conclusions: The multigene signature showed potential for tailoring adjuvant chemotherapy for patients with operable triple negative breast cancer. Intensive regimens incorporating gemcitabine and cisplatin into anthracycline/taxane based therapy significantly improved disease-free survival with manageable toxicity., Trial Registration: ClinicalTrials.gov NCT02641847., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the National Key Research and Development Project of China, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Shanghai Key Laboratory of Breast Cancer, SHDC Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals, and CSPC Pharmaceutical Co Ltd, Shijiazhuang, China, for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: De-escalating anthracycline is gaining popularity for breast cancer patients. We aim to evaluate the non-inferiority of an anthracycline-free or short-term regimen to the standard anthracycline-based regimen for operable patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer., Methods: It is a prospective, open-label, phase 3, randomized non-inferiority trial from June 1, 2010 to June 1, 2017. Follow-up had been kept until July 2019. This trial was conducted at Fudan University Shanghai Cancer Center. Patients with pT1-3N+ or pT2-3N0 but high-risk (grade II/III, lymphovascular invasion, ≤35 years of age or hormone-receptor negative) HER2-negative operable breast cancer were eligible and stratified by age, pathological tumour stage, pathological node status and hormone-receptor status. Patients were randomized to 6 cycles of docetaxel and cyclophosphamide (TC, n  = 524), 3 cycles of cyclophosphamide/epirubicin/fluorouracil followed by 3 cycles of docetaxel (CEF-T, n  = 523) or epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks (EC-P, n  = 524) as the intention-to-treat population. Of these patients, 94% completed allocated therapy. Difference in disease-free survival (DFS) compared to EC-P. The prespecified non-inferiority margin was 4.5%, corresponding to the hazard ratio (HR) of 1.44 (one-sided α = 0.05), with an assumed 5-year DFS of 89% for EC-P., Findings: Included in the intention-to-treat population were 1571 patients (median [IQR] age, 50 [45-57] years; 92% estrogen receptor [ER]-positive; 59% pN+). Through a median follow-up of 5.5 years, HR for TC versus EC-P was 1.05 (5-year DFS: 85.0% vs . 85.9%; 90% confidence interval [CI]: 0.79-1.39, non-inferior P  = 0.048) and for CEF-T versus EC-P, 0.99 (5-year DFS: 85.1% vs . 85.9%; 90% CI: 0.75-1.30, non-inferior P  = 0.045). Grade 3 or 4 adverse events for TC included rash (3.9%) and peripheral neuropathy (2.8%) and for CEF-T and EC-P diarrhea and nausea/vomiting were predominant. Results of per-protocol analyses were similar., Interpretation: Both TC and CEF-T are non-inferior adjuvant regimen to EC-P mainly in patients with ER+HER2- breast cancer. TC is a safe regimen that avoids anthracycline-related side effects., Funding: This work was supported by grants from the National Natural Science Foundation of China (Grants 81672600, 81722032, 82072916, and 91959207), the 2018 Shanghai Youth Excellent Academic Leader, the Fudan ZHUOSHI Project, the Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (grant SHDC12010116), the Cooperation Project of Conquering Major Diseases in the Shanghai Municipality Health System (grant 2013ZYJB0302), the Innovation Team of the Ministry of Education (grant IRT1223), and the Shanghai Key Laboratory of Breast Cancer (grant 12DZ2260100) and the National Cancer Institute (grant P30 CA16058)., Competing Interests: The authors have declared no conflicts of interest., (© 2021 The Author(s). Published by Elsevier Ltd.)

Purpose: The function of long noncoding RNAs (lncRNA) in breast cancer metastasis remains largely unknown. In this work, the role of HOXC-AS3 in breast cancer progression was investigated. Methods: By using Cancer Genome Atlas (TCGA) Database, we investigated the expression of HOXC-AS3 in breast cancer and explored the association between HOXC-AS3 expression and prognosis. Then, we studied the biological function of HOXC-AS3 in cell migration and invasion both in vitro and in vivo . Furthermore, the target miRNA of HOXC-AS3, and the target mRNA of miR-3922-5p were proved. Results: HOXC-AS3 is aberrantly overexpressed in breast cancers especially the HER2 + type. Moreover, high expression of HOXC-AS3 has a relationship with poor clinical outcomes of breast cancer. In addition, HOXC-AS3 regulates cell Invasion and migration both in vitro and in vivo . Our results demonstrated that miR-3922-5p was a direct target of HOXC-AS3, and PPP1R1A was a target of miR-3922-5p in breast cancer. Conclusions: The novel lncRNA HOXC-AS3 acts as a miR-3922-5p sponge to upregulate PPP1R1A protein expression, and thus results in promoting breast cancer metastasis. HOXC-AS3 could be a novel therapeutic target for breast cancer therapeutics.

As a topical plaster developed by modern pharmaceutical technology based on traditional Tibetan medicine,Cheezheng Xiaotong Tiegao has functions of promoting blood circulation,relieving swelling and relieving pain. Since its introduction in 1993,it has been widely used in the treatment of various types of acute and chronic musculoskeletal pain and various types of spinal,joint and soft tissue diseases. In order to better standardize the clinical application and improve the clinical efficacy of Cheezheng Xiaotong Tiegao,the research and development work of the Experts consensus statement on Cheezheng Xiaotong Tiegao in clinical practice was officially launched on October 19,2017,upon approval from China Association of Chinese Medicine. In this paper,main R&D process and related technical links for the experts consensus on Cheezheng Xiaotong Tiegao would be summarized,which will help the various medical workers understand,master and apply more accurately,and also provide reference for the development of experts consensus on clinical application of other topical Chinese medicines.

Breast cancer is one of the most common malignancies in women. Current treatment of breast cancer is mainly based on clinicopathological characteristics, and is not sufficiently customized for individual cases. The concept of genotyping in breast cancer was first proposed in 2001. Five major genotypes of breast cancer have been identified and their study has given rise to a new field of research. In our study, we investigated the expression of 13 chemokines and chemokine receptors, which play important roles in inflammation and tumor progression, in five breast cancer genotypes. Using immunohistochemistry, we found that CCL2 expression was significantly different between the different breast cancer genotypes and was negatively associated with estrogen and progesterone receptor expression. Kaplan Meier analysis showed that a low expression of CCL2 was associated with better outcome in breast cancer patients. Enzyme-linked immunosorbent assay results revealed that CCL2 expression in different breast cancer genotype cell line suspensions was significantly different.

The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor implicated in multiple cellular processes and its expression has been shown to play a critical role in tumorigenesis. However, the role of AhR in tumorigenesis of breast cancer remains unclear. In the current study, we investigated the expression levels of AhR in breast lesions and assessing the correlation between AhR expression and clinicopathological variables using breast cancer tissue microarray. Meanwhile, 10 paired of fresh breast cancer and corresponding non-cancer samples were detected for AhR and p53 expression by Western blot, respectively. Results showed that AhR expression levels in breast cancer tissues were significantly higher than that in the non-cancer tissues. AhR expression was associated with the pathological type and P53 status, but not patients age, tumor grade and TNM, as well as ER, PR, C-erbB2, Ki-67, AR, EGFR status. Moreover, Western blot data suggested a negative correlation between p53 protein and AhR protein expression levels. The results suggest that high levels of AhR were expressed in the majority of breast cancer tissues and closely associated with P53 status and histological types of breast cancer. AHR and its abnormal expression may play an important role in multiple stages of breast cancer progression.

Objective: To explore the effects of hsa-miR-206 on the proliferation, migration and invasion of breast cancer., Methods: The hsa-miR-206 mimics, inhibitors and their paired negative controls were transfected into human breast cancer cell line MDA-MB-231 by liposome. The proliferation of cell was evaluated by CCK-8 and the migration and invasion was detected by Transwell. Matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), breast cancer metastasis-suppressor 1 (BRMS-1) and connexin 43 (Cx43) were detected by both quantitative polymerase chain reaction (qPCR) and Western blot. The expression of miR-206 was detected by qPCR. Dual luciferase assay was detected to confirm the specific binding sites of miR-206 and Cx43., Results: (1) The proliferation activity of 206m-group cell (0.74 ± 0.16) was significantly lower than that of control group (1.12 ± 0.23) (t = -3.066, P = 0.037) while that of 206i-group cell (1.43 ± 0.26) was higher than that of control group (0.98 ± 0.14) (t = 3.635, P = 0.022). (2) Transwell tests showed the migration and invasion of 206m-group cell decreased significantly (migration:0.56 ± 0.01 vs 0.63 ± 0.01, t = -23.00, P = 0.002; invasion:0.79 ± 0.01 vs 0.99 ± 0.01, t = -21.200, P = 0.002), but that of 206i-group cell increased significantly (migration:0.97 ± 0.11 vs 0.61 ± 0.09, t = 32.787, P = 0.001; invasion:1.10 ± 0.01 vs 0.93 ± 0.05, t = 5.167, P = 0.035). (3) The expressions of MMP-2,MMP-9 and Cx43 decreased and the expression of BRMS-1 increased in 206m-group cell and vice versa in 206i group. (4) The expression of miR-206 in lymph node-negative group of clinical breast cancer sample was higher than that of lymph node-positive one. And there was statistical difference (Z = -2.098, P = 0.003). And the expression of Cx43 was opposite. (5) Dual luciferase reporter assay confirmed the specific binding sites of hsa-miR-206 and Cx43., Conclusion: Hsa-miR-206 has negative controls of proliferation, migration and invasion of breast cancer cell by targeting Cx43.

Objective: To investigate the relationship between LKB1 gene and invasion of breast cancer cells., Methods: Human breast cancer cells of the line MDA-MB-435 were cultured and transfected with plasmids with or without LKB1 gene. The clone of the transfected MDA-MB-435 cells with high expression of LKB1 was called MDA-MB-435/LKB1 (H), and that with low expression of LKB1 was called MDA-MB-435/LKB1 (L). The MDA-MB-435 cells transfected with blank vector was called MDA-MB-435/vec. MDA-MB-435 cells without transfection were used as controls. RT-PCR was used to detect the mRNA expression of the invasion-related factors of breast cancer: matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF), and Western blotting was used to detect the protein expression of these factors. Gelatin zymography was used to expression of the secretive MMP-2 and MMP-9. Transwell test was used to examine the membrane penetration of the different MDA-MB-435 cells., Results: The invasion rate was (47.6 +/- 1.3)% in the MDA-MB-435 cells, (45.6 +/- 1.2)% in the MDA-MB-435/vec cells, both significantly higher than those of the MDA-MB-435/LKB1 (H) and MDA-MB-435/LKB1 (L) cells [(18.1 +/- 1.0)% and (22.4 +/- 1.8)% respectively, all P < 0.01], with significant difference between the latter 2 groups (P < 0.05). The mRNA expression and protein expression of MMP-2, MMP-9, VEGF, and b-FGF were all significantly lower in the MDA-MB-435/LKB1 cells. Gelatin zymography showed that the secretive MMP-2 and MMP-9 were expressed at the protein level significantly lower in the MDA-MB-435/LKB1 cells., Conclusion: LKB1 gene inhibits the invasion of breast cancer cells.