Neoadjuvant therapy is a preoperative systemic treatment for patients with breast cancer. This therapy has greatly improved the clinical outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is associated with poor prognosis. Currently, dual anti-HER2 antibodies, including trastuzumab and pertuzumab, combined with non-anthracycline chemotherapy is one of the standard regimens to achieve high pathologic complete response rate and satisfactory efficacy. The combination of trastuzumab with tyrosine kinase inhibitors, antibody-drug conjugate drugs, or immunotherapy combined with target therapy, under the indications of reasonable biomarkers, is effective for HER2-positive breast cancer. In this article, we briefly reviewed neoadjuvant therapy in the dual-targeting therapy era and discussed its future perspectives.

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
Cattle ; Animals ; Mice ; Bacterial Proteins/metabolism* ; Bacillus cereus/metabolism* ; Hemolysin Proteins/metabolism* ; Virulence Factors/metabolism* ; Enterotoxins/metabolism*

Triple-negative breast cancer (TNBC) accounts for approximately 15%–20% of all breast cancers. Patients with TNBC have a rapidly progressive clinical course, an earlier age of onset, faster distant recurrence, and more common visceral metastases as compared with other subtypes. However, treatment of TNBC is often limited to chemotherapy and has a poor prognosis. Therefore, developing the best treatment strategy for patients is essential to reduce the burden of disease caused by TNBC. Various potential available drug targets have been discovered, as well as precision treatment and classified treatment are changing the clinical practice of TNBC, thereby indicating a new therapeutic area for TNBC in addition to traditional chemotherapy. This article reviews the systemic treatment options for TNBC in recent years, including immunotherapy and targeted therapy.

Female ; Humans ; Breast Neoplasms/surgery* ; Inflammatory Breast Neoplasms ; Mastectomy ; Medical Oncology

Objective To analyze the efficacy and safety of trastuzumab (H) and pertuzumab (P) combined with different chemotherapy regiments in neoadjuvant therapy for HER2-positive breast cancer. Methods We retrospectively analyzed the clinical data of the patients with HER2-positive breast cancer who received HP combined with chemotherapy as neoadjuvant therapy and completed surgery. The primary endpoint was total pathologic complete response (tpCR) (ypT0/isypN0), the secondary endpoints were breast pathologic complete response(bpCR) (ypT0/is) and axillary pathologic complete response (apCR) (ypN0), and the factors influencing pCR were analyzed. Results A total of 63 patients were included, of whom 23 were treated with TCbHP, 27 were treated with THP regimen, and 13 were treated with AC-THP. The overall tpCR rate was 65.1%, of which TCbHP was 73.9%, THP was 55.6%, and AC-THP was 69.2%. The tpCR rate of HR-negative patients was 79.2%, higher than that of HR-positive 56.4%. The overall bpCR rate was 69.8%, and apCR rate was 81.0%. Univariate analysis showed that HER2 status was a related factor affecting tpCR (P=0.023). The total effective rate by MRI was 87.3%. The level 3 and 4 toxicity of the TCbHP regimen was slightly higher than those of the THP and the AC-THP regimens. Conclusion HP combined with chemotherapy have achieved relatively high pCR. HER2 status is a related factor that affects tpCR. The adverse reactions are controllable.

Objective To investigate the effect of IFN-γ on the proliferation and migration of esophageal squamous cell carcinoma cell line Eca9706 and related mechanism. Methods Cells were cultured in vitro and treated with interferon-γ. Cell morphology changes were observed under microscope, cell proliferation ability was detected by CCK-8 experiment, and cell migration ability was detected by cell scratch experiment and Transwell experiment. Real-time PCR method was used to detect the expression efficiency of chemokine CXCL8 (interleukin 8), and the ELISA experiment was used to detect the change of CXCL8 secretion. Results Compared with the blank control group, Eca9706 cells treated with different concentrations of interferon-γ did not change significantly in cell morphology. CCK8 experiment confirmed that the proliferation ability of Eca9706 cells after IFN-γ treatment was significantly reduced (P < 0.01). Cell scratch experiment found that IFN-γ significantly decreased the migration ability of Eca9706 cells (P < 0.01). Transwell experiment showed that after IFN-γ treatment, the migration ability of Eca9706 cells was significantly inhibited (P < 0.01). CXCL8 gene expression level in Eca9706 cells treated with interferon-γ was significantly down-regulated (P < 0.01), and the amount of CXCL8 secretion significantly reduced (P < 0.05). Conclusion Interferon-γ can inhibit the proliferation and migration of esophageal cancer cell line Eca9706, which may be related to its inhibition of the expression and secretion of CXCL8.

Objective To explore the prognostic factors of the pathological complete response of internal mammary lymph node (ipCR) after neoadjuvant chemotherapy and its effect on breast cancer prognosis. Methods We retrospectively analyzed the clinical data of 70 patients with primary breast cancer with internal mammary lymph node metastasis who received neoadjuvant chemotherapy. Patients were divided into the ipCR group and non-ipCR group based on their postoperative pathology. χ² test, Fisher, and Logistic regression were used for univariate and multivariate analysis. Meanwhile, the Kaplan-Meier curve and Cox regression were used for prognostic analysis. Results Of 70 patients, 31 obtained ipCR (44.3%). Univariate analysis showed that the expression levels of apCR, HR, and HER2 status were related to ipCR (P < 0.05). Multivariate analysis showed that age, apCR, and HER2 status were independent predictors of ipCR (P < 0.05). The average DFS of ipCR group was better than non-ipCR group (96.0 vs. 67.1 months, P < 0.05). The risk of recurrence and metastasis was 87% lower in the ipCR group than in the non-ipCR group (HR=0.13, 95%CI: 0.04-0.44, P < 0.01). ipCR, Ki67 expression level, and breast pCR (bpCR) were independent factors affecting patients' prognosis. Conclusion There is a correlation between clinico pathological factors and ipCR after neoadjuvant chemotherapy. ipCR can be used to predict the prognosis of patients with internal mammary lymph node metastasis.

Objective To systematically evaluate the risk of primary lung cancer in breast cancer patients. Methods A computer-based search was conducted for the English literatures about the risk of primary lung cancer in breast cancer patients in Medline, Scopus and Embase databases. Two researchers independently screened the literatures, extracted the data and assessed the risk of bias. The statistical analysis was performed using the Stata 15.5 software. Results A total of 7 references were included, and the overall risk of primary lung cancer in female breast cancer patients was slightly higher than that in the general population (SIR: 1.18, 95%CI: 1.09-1.27). Subgroup analysis showed that the risk of lung cancer was significantly increased in women aged < 50 years after diagnosis of breast cancer (SIR: 1.99, 95%CI: 1.48-2.69). Conclusion Compared with the general population, the risk of primary lung cancer is increased in female breast cancer patients, especially in young women with breast cancer.

TET1 has been discovered capable of promoting DNA demethylation by mediating 5-methylcytosine to inhibit the genesis and development of cancer.Epithelial-Mesenchymal transition is a complex cellular program in cancer progression and metastasis,whose hallmark is loss of cell polarity and cell adhesion and acquirement of migration and invasion abilities,leading tumor cells into blood vessel and lymphatic vessels to form new metastatic lesions.Epigenetics plays a vital role in epithelial-mesenchymal transition.This review focuses on the relationship of TET1,epigenetics and epithelial-mesenchymall transition,and the research progression of TET1's role in cancer invasion and metastasis.