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Human epidermal growth factor receptor-2 （HER-2）-positive breast cancer has higher predilection to metastasize and invade other organs， leading to poor prognosis. The anti-HER-2 drugs， such as trastuzumab， pertuzumab， and trastuzumab emtansinehas， can remarkably prolong the disease free survival （DFS） of patients. However， frequent multidrug resistance， tumor recurrence and metastasis， and adverse reactions such as cardiotoxicity and gastrointestinal discomfort caused by adjuvant therapy are still challenges for the treatment of HER-2-positive breast cancer. The understanding of breast cancer in traditional Chinese medicine （TCM） has a long history. In thousands of years of inheritance and innovation， a standardized treatment system with TCM characteristics has been gradually formed， which shows unique advantages and significant curative effects in breast cancer treatment. The treatment principles of ''treatment based on syndrome differentiation''， ''treatment based on stages and types''， ''treatment according to individual conditions''， and ''treatment of different viscera and viscera based on the toxin and pathogen'' are closely related to the precise treatment concept. In view of the challenges in the treatment of HER-2-positive breast cancer， such as multidrug resistance， tumor recurrence and metastasis， cardiotoxicity， and gastrointestinal discomfort， this paper summarizes the characteristics of TCM in reversing the multidrug resistance， inhibiting tumor recurrence and metastasis， prolonging DFS， improving prognosis， reducing adverse reactions caused by adjuvant therapy， and improving the quality of life after breast cancer surgery according to the principles of reinforcing healthy Qi and eliminating pathogen， and treatment based on syndrome differentiation. This article is expected to serve as a reference for TCM treatment of HER-2 positive breast cancer.
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@# The efficacy and prognosis of human epidermal growth factor receptor 2 (HER2) positive breast cancer patients have been significantly improved with the development and wide application of anti-tumor drugs against HER2. The results of PEONY research once again established the status of the double-target treatment mode of pertuzumab+trastuzumab in the field of neoadjuvant therapy. Based on the two studies of TRYPHAENA and TRAIN-2, paclitaxel plus platinum should be the first choice chemotherapy scheme for anti HER2 double-target therapy, and the treatment course of 6 cycles is preferred. According to the consensus of neoadjuvant therapy experts in China and the latest follow-up results of adjuvant APT study, the neoadjuvant therapy is more suitable for patients with a tumor diameter of more than 3 cm and/or positive lymph nodes metastasis; T-DM1 should be the first choice of adjuvant therapy in patients, who didn’t obtain pCR after neoadjuvant treatment, and whether the double-target adjuvant mode of pertuzumab plus trastuzumab is suitable depends on follow-up of the PEONY study. Low-risk patients with small tumors (<3 cm) and without lymph node metastasis may consider omitting neoadjuvant therapy but adopt direct surgery followed by postoperative adjuvant therapy with trastuzumab plus paclitaxel. The regimen of trastuzumab+pertuzumab combined with taxanes is still the standard first line treatment of late stage HER2+ patients; for Chinese patients, pyrotinib combined with capecitabine can be used as the second line optimization, and T-DM1 can be used as the third line and posterior line selection; when trastuzumab, pertuzumab and T-DM1 fail the treatment, DS-8201 becomes a new selection mode. Combined treatment mode of tucatinib plus trastuzumab and capecitabine can be considered in late stage HER2+ patients with brain metastases.
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The aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis. We investigated the impacts of overexpressed miR-455 on the proliferation and invasiveness of MDA-MB-453 cells and measured its effects on the expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-455 was significantly and positively correlated to the prognosis and overall survival (OS) of the BC (P=0.028), according to TCGA information. The expression level of miR-455 was positively correlated with OS and relapse-free survival (RFS) of patients with Her-2-positive BC, and was negatively correlated with the number of metastatic lymph nodes (P<0.05). Transwell assay suggested that MDA-MB-453 cells became much less invasive (P<0.01) after being transfected with miR-455 mimics. During the qRT-PCR, the expression level of MALAT1 declined significantly after transfection (P<0.01). Overexpressed miR-455 significantly inhibited the proliferation and migration of MDA-MB-453 cells and the expression of MALAT1. We conclude that miR-455 may be a useful potential biomarker for forecasting lymph node metastasis and the prognosis of Her-2-positive BC patients. miR-455 may play an important role in lymph node metastasis of BC by interacting with MALAT1.
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The human epidermal growth factor receptor 2 (HER2) ERbb2 gene is amplified in approximately 25% of breast cancers. Characteristics of HER2-amplified tumors include increased proliferation rates and a propensity for distant metastasis. The discovery of overexpression of HER2 in a subset of breast cancers was an important milestone in our understanding of the biology of the disease. This paved the way for the discovery of trastuzumab, a humanized monoclonal antibody targeting HER2. Trastuzumab is the foundation of treatment of HER2- positive breast cancers, demonstrating dramatic responses in patients with metastatic disease. Recent advances in our understanding of the interaction between HER2 and other members of the epidermal growth factor receptor family have led to the identification of newer agents, resulting in the expansion of the clinical armamentarium of available agents for the treatment of HER2-positive tumors. The biology of the ERbb receptor family, the use of HER2-targeted agents in breast cancer, and the advances in anti-HER2 agents that are currently in clinical development are reviewed here.
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Objective: To investigate effect of Yanghe Huayan Tang and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 in intervening expressions of human epidermal growth factor receptor human epidermal growth factor receptor-2(HER-2), PI3K and phosphorylated serine/threonine kinase (p-Akt)in PI3K/Akt pathway of breast cancer cell line SK-BR-3 (HER-2 high expression) in vitro, and study intervention mechanism of Yanghe Huayan Tang. Method: Yanghe Huayan Tang intestinal absorption fluid was prepared, breast cancer cell strain SK-BR-3 was divided into blank group, Yanghe Huayan Tang group, LY294002 group, LY294002+Yanghe Huayan Tang group. The concentration was respectively 125 g·L-1 for Yanghe Huayan Tang, 0.05 g·L-1 for LY294002, 125 g·L-1 for Yanghe Huayan Tang+LY294002.The expressions of HER-2, PI3K and p-Akt protein were detected by immunohistochemistry and Western blot after 24 h. The most appropriate and effective concentration was obtained through extensive experiments. The expressions of HER-2, PI3K and p-Akt were detected by reverse transcription polymerase chain reaction (RT-PCR). Result: Compared with blank group, LY294002 group, and LY294002+Yanghe Huayan Tang group could inhibit protein and mRNA expressions of HER-2, PI3K, p-Akt in breast cancer cell lines(PPPPConclusion: Yanghe Huayan Tang can inhibit angiogenesis and invasion of breast cancer. Its main mechanism is expressed by intervening PI3K/Akt pathway, reducing expressions of HER-2, PI3K and p-Akt in pathway.
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Objective: To analyze the concordance rates of estrogen receptor (ER),progesterone receptor (PR),human epidermal growth factor receptor-2 (HER-2),and Ki67 statuses between the primary and loco-regional recurrence (LRR) lesions and its influence on the following treatment in breast cancer patients. Methods: The breast cancer patients undergoing surgery in Comprehensive Breast Health Center,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from January 2009 to September 2018,who were reported recurrence only in loco-regional site were retrospectively analyzed. ER,PR,HER-2,and Ki67 statuses were detected in primary and LRR lesions. Concordance rates and their influence on following treatment were further analyzed. Results: A total of 7 823 breast cancer patients received surgery,among whom 106 cases experienced LRR without distant metastasis. There were 56 patients having full information about ER,PR,HER-2,and Ki67 statuses of LRR lesions,with the positive rates of 48.2%,25.0%,35.2%,and 81.5%,respectively. Concordance rates of ER,PR,HER-2,and Ki67 between primary and LRR lesions were 76.8%,76.8%,89.1% and 77.8%,with κ values at 0.538,0.469,0.729,and 0.402,respectively. Hormone receptor (ER or PR) (14 cases) and/or HER-2 (6 cases) statuses were altered in 18 patients. The hormone receptor status changed from positive to negative in 9 cases,of which 4 cases did not receive following endocrine therapy. The HER-2 status changed from negative to positive in 4 patients,and 1 of them received following anti-HER-2 targeted therapy. Conclusion: The concordance rates between primary and LRR breast cancer lesions of ER,PR,and Ki67 are moderate,and the concordance rate of HER-2 is high. Changes in receptor status in LRR lesions may affect the choice of following treatment options.
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Human epidermal growth factor receptor (HER)-2-positive breast cancer is a type of highly invasive breast cancer with a high recurrence rate. Although the single-targeted treatment for HER-2 prolongs survival, patients still develop recurrence and metas-tasis. The mechanisms of dual-targeted therapies are non-overlapping and have synergistic effects, which further improves the survival of patients. Based on trastuzumab, this article reviews the current status and progression indual-targeted therapeutic regimens con-taining anti-HER-2.
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Objective: To investigate the relationship between tumor-infiltrating lymphocytes (TILs) and the androgen receptor (AR) in human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. Methods: Specimens of 448 patients with HER-2-positive breast cancer from the Tianjin Medical University Cancer Hospital between March 2018 and November 2018 were collected. TILs were pathologically evaluated. AR expression was immunohistochemically analyzed. The relationships among TILs, the AR, and clinicopathological parameters were determined. Results: There were 38.2% (171/448) patients with TILs non/low-infiltrated, 42.2% (189/448) with moderately infiltrated, and 19.6% (88/448) with high infiltration. AR was positive in 62.7%(281/448) of the patients. Spearman correlation analysis showed that TILs and the AR were negatively related (r=-0.140, P=0.003). TILs were significantly associated with the AR in estrogen receptor positive breast cancer (P=0.009). Conclusions: TILs and the AR were negatively related in HER-2-positive breast cancer, indicating that HER-2-positive breast cancer can be treated according to the different infiltration levels of TILs and AR expression.
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Human epidermal growth factor receptor-2 (HER-2) gene amplification and protein overexpression occur in approximately 15% to 20% of breast cancer patients, resulting in a clinically aggressive tumor type that is associated with a poor prognosis. HER-2-tar-geted therapies could effectively reduce the recurrence and improve the prognosis of breast cancer. In recent years, the application of new anti-HER-2 agents, such as pertuzumab, T-DM1, and pyrotinib, have further improved the survival of patients with HER2-positive breast cancer, and updated the guidelines for the treatment of breast cancer, making anti-HER-2 targeted therapy more accurate. This review described the latest development of targeted agents for HER-2-positive breast cancer.
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@# Objective: To modify traditional prognostic model for patients with ER/PR+, HER2- breast cancer to meet the actual requirements in current clinical practice. Methods: 335 patients with ER/PR+, HER2- breast cancer, who were admitted in Department of Breast Surgery, Shanghai Huangpu Center Hospital from January 2009 to December 2009, were enrolled in this study. 97 variables were incorporated into the model, using SCAD variable selection method, after fully considering whether covariates existing a log-linear relationship, reasonable determination of the cut-off value of the covariates in non-logarithmic linear relationship (piecewise linear relationship) and collinear and interaction, then we set up a new Cox regression prognostic model for traditional ER/PR+, HER2-type breast cancer patients with traditional immunohistochemical indicators, and further establish its nomogram model. On this basis, a nomogram of the survival probability of 1-, 3-, and 5- years after surgery was established; The discrimination and calibration of model were compared to evaluate the predictive ability of the model. Results: The Cox regression model shows that the prognosis of patients are associated with the histologic grade, lymph node metastasis, Ki67, PR and age etc. Among them, the histologic grade and lymph node metastasis have log-linear relationship with prognosis; Ki67, PR and age have non-log-linear relationship with prognosis and the reasonable cut-off values are Ki67(60%)，PR（20%）and age（55 years old） . Area under the receiver operating characteristic (ROC) curve（AUC）of this Cox model for 1-, 3- and 5- year survival after surgery are all above 0.85, indicating high discrimination. The Grønnesby-Borgan goodness-of-fit test statistics of this model is 1.37 with P>0.05, indicating good calibration. Conclusion: The modified nomogram.could accurately, directly and effectively predict the survival probability of patients, which may exert good guidance for the clinical practice for patients with breast cancer.
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@#[Abstract] Objective: To investigate the relationship between expression of MICA/B (MHC class I chain-related proteinA/B) and disease-free survival (DFS) of patients with HER2+(human epidermal growth factor receptor 2) breast cancer tissue. Methods: Twenty six cases of corresponding para-cancerous tissue and 100 cases of HER2+ breast cancer tissue that preserved in wax at Zhengzhou People’ s Hospital Affiliated to Southern Medical University from January 2009 to June 2010 were collected for this study. Expression of MICA/ B in these tissue samples was detected by immunohistochemistry; and the relationship between MICA/B expression with clinicopathologic features as well as DFS was analyzed with Kaplan-Meier survival curve. Results: The expression of MICA/B in adjacent paracancerous tissues was negative (0/26), however, it was highly positive in cancer tissues (92/100), and the percentage with high expression was 65%(65/100), the difference was significant (P<0.05). High MICA/B expression rate in stage I was significantly higher than that in stage Ⅱ-Ⅲ (77.55% vs 52.94%， P<0.05), and the high expression rate in stage T1 was also significantly higher than that in stage T2-T4 (75.00% vs 52.27%， P<0.05). High MICA/B expression rate in ER+, PR+ group (with positive number≥1%) was significantly lower than that in ER- , PR-group (ER： 52.38% vs 74.14%，PR： 51.35% vs 73.02%， all P<0.05). MICA/B expression was correlated with clinical stages, the expression of ER, PR and tumor size (all P<0.05), but not associated with menopausal status, histological grade and lymph node metastasis (all P>0.05). Over-expression of MICA/B was closely associated with much better 6-year DFS rate in patients no matter with or without targeted therapy (the targeted group: 90.6% vs 72.2%; the untargeted group: 78.4% vs 58.8%, all P<0.05). Conclusion: Over-expression of MICA/B in HER2+ breast cancer tissue is closely related to DFS, which may be served as a potential prognosis indicator for patients with HER2+ breast cancer.
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Breast cancer is one of the most common malignancies happened in female patients.The incidence of breast cancer in Chinese females has increased in recently years.Human epidermal growth factor receptor-2 (HER-2) exhibits gene amplification or high expression of receptor protein in about one third of breast cancer patients.HER-2 positive breast cancer patients has poor prognosis,high risk of recurrence and short survival.Trastuzumab is a specific inhibitor of human epidermal growth factor receptor-2 [1],which has been widely used in the treatment of HER-2-positive breast cancer patients,and trastuzumab molecular targeting therapy compared with the traditional chemotherapy,with the advantages of high specificity and low toxicity.It changes the natural disease progression of patients with HER-2-positive breast cancer and prolongs the patient's survival time.This article will review the researches on the four aspects,which including the development and the application of trastuzumab in the treatment of HER-2 positive breast cancer.
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Objective To study the correlation of expression of DNA topoisomerase Ⅱ alpha (TOP2A)with expressions of human epidermal growth factor receptor 2 (HER2)and phosphatase and tensin homolog (PTEN)and gene mutation of phosphatidylinositol 3-kinase (PI3K)in breast cancer so as to provide reference for prognosis of the cancer and evaluation of drug efficiency.Methods This study enrolled totally 96 breast cancer patients. Tumor specimens were resected.The gene expressions of TOP2A,HER2 and PTEN were analyzed using branched DNA-liquid-chip,and PI3K gene mutation was detected by xTAG-liquid-chip.Correlations between gene expressions and gene mutation were further explored by Spearman correlation analysis so as to clarify the relationship between TOP2A and HER2 signaling pathway gene.Results Co-expression of TOP2A and HER2 was strong,and TOP2A tended to be highly expressed in the presence of high expression of HER2 (P =0.01).The expression of PTEN was not significantly correlated with the expression of TOP2A,whereas the mutation of PI3K had a positive association with the high expression of TOP2A (P =0.004).Conclusion Anthracycline drug resistance factor TOP2A may be related to the critical factors of HER2 signaling pathway,suggesting that HER2 expression and PI3K mutation may be key factors in regulation of TOP2A expression,which would provide important evidence for chemotherapeutic resistance.
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Objective To analyze the relationship of the expression level of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2, c-erbB-2) of breast invasive ductal carcinoma (IDC) with ultrasonographic characteristics. Methods Totally 104 patients with IDCs confirmed pathologically were involved in this study. ER, PR and c-erbB-2 expression in the IDC specimens was determined by immunohistochemical staining technique. The correlation between the ultrasonographic features and the positive expression of ER, PR or c-erbB-2 was analyzed. Results The positive expression rate of ER and PR in the group with tumor spiculation sign and posterior acoustic attenuation was higher than that in the group without. The positive expression rate of ER differed significantly (P<0.05) while that of PR did not (P>0.05). The over-expression rate of c-erbB-2 in the group of microcalcification, sufficient blood flow and axillary lymph node metastasis was higher than that in the group of non-microcalcification, deficient blood flow or without axillary lymph node metastasis (P<0.05). The expression of ER, PR and c-erbB-2 was not related to the size of tumor (P>0.05). Conclusion The expression of ER and c-erbB-2 is closely related to the ultrasonographic characteristics of IDC, which may, to some extent, reflect the expression level of ER and c-erbB-2.
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Objective: To analyze the relationship of the expression level of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2, c-erbB-2) of breast invasive ductal carcinoma (IDC) with ultrasonographic characteristics. Methods: Totally 104 patients with IDCs confirmed pathologically were involved in this study. ER, PR and c-erbB-2 expression in the IDC specimens was determined by immunohistochemical staining technique. The correlation between the ultrasonographic features and the positive expression of ER, PR or c-erbB-2 was analyzed. Results: The positive expression rate of ER and PR in the group with tumor spiculation sign and posterior acoustic attenuation was higher than that in the group without. The positive expression rate of ER differed significantly (P 0.05). The over-expression rate of c-erbB-2 in the group of microcalcification, sufficient blood flow and axillary lymph node metastasis was higher than that in the group of non-microcalcification, deficient blood flow or without axillary lymph node metastasis (P 0.05). Conclusion: The expression of ER and c-erbB-2 is closely related to the ultrasonographic characteristics of IDC, which may, to some extent, reflect the expression level of ER and c-erbB-2.