Breast cancer is the most common cancer in the world, and 5-year survival rate of metastatic breast cancer is about 20%. The treatment of metastatic breast cancer is mainly chemotherapy, endocrine therapy and targeted therapy. However, after multiline treatment, patients with MBC especially the triple negative breast cancer face the problem of drug resistance. Tumor angiogenesis theory suggests that blocking angiogenesis can inhibit tumor growth and migration. Based on this, angiogenesis treatment strategy is proposed. Antiangiogenic drugs mainly include biological macromolecular drugs targeting vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) and small molecule VEGFR inhibitors. Angiogenesis is known to play a key role in the growth and metastasis of breast cancer. Therefore, anti-angiogenetic therapy has potential in metastatic breast cancer patients. Since the approval of tumor drug indications by NPMA in China is often later than the release of the latest research data, the National Health Commission issued "the guiding principles for the clinical application of new antitumor drugs" in 2020. The principle pointed out that under special circumstances such as the absence of better treatment, medical institutions should manage the usage of drugs that are not clearly defined in the instructions but have evidence-based data. Based on the latest research progress in breast cancer, the consensus writing expert group collated published reports, international academic conferences, conducted analysis, discussion and summary, collected data on the use of small molecule anti-vascular targeting drugs for advanced breast cancer, and formulated "expert consensus on the application of small molecule anti-angiogenic drugs in the treatment of advanced breast cancer" . For clinicians' reference only.
Angiogenesis Inhibitors/therapeutic use* ; Breast Neoplasms/pathology* ; Consensus ; Female ; Humans ; Neovascularization, Pathologic/pathology* ; Off-Label Use ; Vascular Endothelial Growth Factor A/metabolism*

Breast cancer,one of the common malignant tumors in women,has shown rising incidence in recent years,posing a serious threat to women's health.The advancement of molecular biology facilitates the revealing of the relationships between signaling pathways and breast cancer.Fibroblast growth factor receptor (FGFR) signaling pathway plays an important role in the proliferation,survival,differentiation,migration,and apoptosis of breast cancer cells.Strategies targeting the FGFR signaling pathway thus exhibit a promising prospect in breast cancer treatment.
Apoptosis ; Breast Neoplasms/metabolism* ; Female ; Humans ; Receptors, Fibroblast Growth Factor/metabolism* ; Signal Transduction

OBJECTIVE: To examine the expressions of JMJD3, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in invasive ductal breast carcinoma, their association with the clinicopathological features of the patients and the effect of JMJD3 overexpression on proliferation and MMP-2 and VEGF expressions in breast cancer cells. METHODS: The protein and mRNA expressions of JMJD3, MMP-2, and VEGF in invasive ductal breast carcinoma and paired adjacent tissues were detected by immunohistochemistry and RT-PCR, respectively, and their correlation with the clinicopathological characteristics of the patients was analyzed. Kaplan-Meier survival analysis was used to evaluate the correlation of JMJD3, MMP-2 and VEGF expression levels with the survival of the patients. In breast cancer MDA-MB-231 cells transfected with a JMJD3-expression plasmid, the expression of Ki67 was examined immunohistochemically, the cell proliferation was assessed with CCK8 assay, and the mRNA expressions of MMP-2 and VEGF were detected with RT-PCR. RESULTS: Breast cancer tissues had significantly lower JMJD3 expression and higher MMP-2 and VEGF expressions at both the mRNA and protein levels than the adjacent tissue ( CONCLUSIONS The expressions of JMJD3, MMP-2 and VEGF in invasive ductal breast carcinoma are closely correlated to tumor proliferation, invasion, metastasis and prognosis and can be used for prognostic evaluation of breast cancer.
Breast Neoplasms/genetics* ; Carcinoma, Ductal, Breast/genetics* ; Humans ; Jumonji Domain-Containing Histone Demethylases ; Lymphatic Metastasis ; Matrix Metalloproteinase 2 ; Prognosis ; Vascular Endothelial Growth Factor A

breast lesions and in predicting the biological characteristics of invasive breast cancer.MATERIALS AND METHODS: Between January 2016 and February 2019, this study included 368 women with 368 pathologically proven breast lesions, which appeared as poor-quality regions in the QM of SWE. To measure shear-wave velocity (SWV), seven regions of interest were placed in each lesion with and without QM guidance. Under QM guidance, poor-quality areas were avoided. Diagnostic performance was calculated for mean SWV (SWV(mean)), max SWV (SWV(max)), and standard deviation (SD) with QM guidance (SWV(mean) + QM, SWV(max) + QM, and SD + QM, respectively) and without QM guidance (SWV(mean) − QM, SWV(max) − QM, and SD − QM, respectively). For invasive cancers, the relationship between SWV findings and biological characteristics was investigated with and without QM guidance.RESULTS: Of the 368 women (mean age, 47 years; SD, 10.8 years) enrolled, 159 had benign breast lesions and 209 had malignant breast lesions. SWV(mean) + QM (3.6 ± 1.39 m/s) and SD + QM (1.02 ± 0.84) were significantly different from SWV(mean) − QM (3.29 ± 1.22 m/s) and SD − QM (1.46 ± 1.06), respectively (all p < 0.001). For differential diagnosis of breast lesions, the sensitivity and areas under the receiver operating characteristic curve (AUC) of SWV(mean) + QM (sensitivity: 89%; AUC: 0.932) were better than those of SWV(mean) − QM (sensitivity, 84.2%; AUC, 0.912) (all p < 0.05). There was no significant difference in sensitivity and specificity between SD + QM and SD − QM (all p = 1.000). Among the biological characteristics of invasive cancers, lymphovascular involvement, axillary lymph node metastasis, negative estrogen receptor status, negative progesterone receptor status, positive human epidermal growth factor receptor status, and aggressive molecular subtypes showed higher SWV(mean) + QM (all p < 0.05), while only lymphovascular involvement showed higher SWV(mean) − QM (p = 0.036).CONCLUSION: The use of QM in SWE might improve the diagnostic performance for breast lesions and facilitate prediction of the biological characteristics of invasive breast cancers.]]>
Area Under Curve ; Breast Neoplasms ; Breast ; Diagnosis ; Diagnosis, Differential ; Elasticity Imaging Techniques ; Estrogens ; Female ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; ROC Curve ; Sensitivity and Specificity ; Ultrasonography

PURPOSE: Trastuzumab is an effective treatment for human epidermal growth factor receptor 2 (HER2)-amplified breast cancers. We sought to develop a simple protocol for HER2 image analysis of breast cancer specimens. MATERIALS AND METHODS: In a preliminary test, we found that at least 1000 tumor cells need to be examined in the most strongly stained areas. Next, we evaluated the clinical usefulness of this established protocol of image analysis in 555 breast cancer patients. Results of the HER2 immunohistochemical (IHC) staining were compared between manual scoring and image analysis. RESULTS: The HER2 IHC results obtained by the image analysis method correlated well with those obtained by the manual scoring method (Cohen's kappa=0.830). Using the HER2 silver in situ hybridization (SISH) results as a gold standard, sensitivity values were 72.1% for manual scoring and 74.0% for image analysis; specificity values were 96.2% for manual scoring and 94.7% for image analysis; and accuracy values were 91.7% for manual scoring and 90.8% for image analysis. McNemar's test was applied to the results, and there were no statistically significant differences in sensitivity and specificity between the positive (p=0.688) and negative (p=0.118) SISH groups. CONCLUSION: HER2 image analysis results were similar to those obtained via the manual scoring method, indicating that the use of image analysis can reduce assessment time and effort. We suggest that image analysis-based evaluation of 1000 tumor cells in the most strongly IHC-stained area, regardless of stroma content, is sufficient for determining HER2 expression levels in breast cancer specimens.
Breast Neoplasms ; Breast ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Methods ; Receptor, Epidermal Growth Factor ; Research Design ; Sensitivity and Specificity ; Silver ; Trastuzumab

PURPOSE: The purpose of this study was to evaluate the risk of central nervous system (CNS) failure in Korean patients with human epidermal growth factor receptor 2 (HER2)-enriched breast cancer treated with surgery followed by postoperative radiotherapy (RT). METHODS: A total of 749 patients from eight institutions were enrolled in this study. All of them underwent surgery followed by postoperative RT from 2003 to 2011; 246 (32.8%) received neoadjuvant chemotherapy and 649 (81.7%) received adjuvant chemotherapy. Adjuvant trastuzumab was administered to 386 patients (48.6%). RESULTS: The median follow-up duration was 84 (range, 8–171) months. The 7-year disease-free and overall survival rates were 79.0% and 84.2%, respectively. On multivariate analysis, mastectomy, nodal involvement, and presence of lymphatic invasion were correlated with poor overall survival (p = 0.004, 0.022, and 0.011, respectively), whereas T stage and lymphatic invasion were associated with disease-free survival (p = 0.018 and 0.005, respectively). Regarding CNS failures, 30 brain metastases, 2 leptomeningeal metastases, and 8 brain and leptomeningeal metastases were noted. The 7-year CNS relapse-free survival rates in patients receiving and not receiving trastuzumab were 91.2% and 96.9%, respectively (p = 0.005). On multivariate analysis, the administration of adjuvant trastuzumab was the only prognostic factor in predicting a higher CNS failure rate (hazard ratio, 2.260; 95% confidence interval, 1.076–4.746; p = 0.031). CONCLUSION: Adjuvant trastuzumab was associated with higher CNS failure rate in Korean patients with HER2-enriched breast cancer. Close monitoring and reasonable approaches such as CNS penetrating HER2 blockades combined with the current standard therapy could contribute to improving intracranial tumor control and quality of life in patients with CNS metastasis from HER2-enriched breast cancer.
Brain ; Breast Neoplasms ; Breast ; Central Nervous System Neoplasms ; Central Nervous System ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Mastectomy ; Multivariate Analysis ; Neoplasm Metastasis ; Quality of Life ; Radiation Oncology ; Radiotherapy ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Survival Rate ; Trastuzumab

PURPOSE: We investigated the prognostic significance of CD9 expression in tumor cells of patients with invasive lobular carcinoma (ILC). METHODS: CD9 expression was evaluated by immunohistochemistry in 113 ILC tissue samples. Correlation of CD9 expression with the patients' clinicopathological parameters and overall survival was assessed. RESULTS: CD9 expression was detected in 48 (42.5%) ILC patients. However, no significant relation could be determined between CD9 expression and the clinicopathological parameters of the patient including tumor size, lymph node metastasis, lymphovascular invasion, histologic grade, expression of hormone receptors, human epidermal growth factor receptor 2 status, and Ki-67 labeling index. Patients with CD9 expression had worse overall survival (p = 0.051) and disease-free survival (DFS, p = 0.014) compared to patients without CD9 expression. Multivariate analysis revealed that CD9 expression was an independent prognostic factor for DFS (p = 0.049). CONCLUSION: CD9 expression in tumor cells could be a significant prognostic marker in patients with ILC.
Breast Neoplasms ; Carcinoma, Lobular ; Disease-Free Survival ; Humans ; Immunohistochemistry ; Lymph Nodes ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor

PURPOSE: The Z0011 trial showed that axillary lymph node dissection (ALND) can be safely avoided in breast cancer patients with low nodal burden (LNB). ALND can be performed in patients with high nodal burden (HNB). We aimed to determine whether HNB in early breast cancer patients can be predicted preoperatively to avoid sentinel lymph node biopsy (SLNB). METHODS: Early invasive breast cancer patients (cT1-2cN0) were retrospectively reviewed. We excluded patients with neoadjuvant chemotherapy and incomplete data. The patients were divided into the following groups based on surgical histology: no positive (N0), LNB, and HNB, defined as 0, 1–2, and ≥ 3 metastatic lymph nodes (LNs), respectively. Of the patients with metastatic nodal disease, only those with ALND were included in the analysis. Clinical, radiological, and histological parameters were evaluated using logistic regression analysis as predictors of HNB versus LNB and N0 combined. RESULTS: Of the 1,298 included patients, 832 (64.1%), 286 (22.0%), and 180 (13.9%) had N0, LNB, and HNB, respectively. Univariate logistic regression analysis revealed that sonographic features of breast tumor size (p < 0.0001), number of abnormal LNs (p < 0.0001), cortical thickness (p = 0.0002), effacement of the fatty hilum (p < 0.0001), and needle biopsy being performed (p < 0.0001) were indicators of HNB. Breast tumor grade (p = 0.0001) and human epidermal growth factor receptor 2 status (p = 0.0262) were also statistically significant. Among these significant features, multivariable stepwise logistic regression showed that the number of abnormal LNs is the sole independent predictor of HNB (p < 0.0001, area under the curve = 0.774). The positive predictive value of HNB in patients with ≥ 4 abnormal LNs was 92.9%. CONCLUSION: The detection of ≥ 4 abnormal LNs on ultrasound can help to identify HNB patients who require upfront ALND and thus avoid SLNB.
Biopsy, Needle ; Breast Neoplasms ; Breast ; Drug Therapy ; Humans ; Logistic Models ; Lymph Node Excision ; Lymph Nodes ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Sentinel Lymph Node Biopsy ; Ultrasonography

Mucinous carcinoma (MC) is a rare subtype of breast cancer, which is composed of tumor cells floating in the abundant extracellular mucin. This form of cancer is usually estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative. Here, we present a case of HER2-positive MC with an unusual signet ring cell differentiation. It is very rare that a breast tumor consists entirely of signet ring cells. The tumor showed pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab and pertuzumab. pCR of HER2-positive MC has rarely been described in literature. It is important to consider the biological heterogeneity of MCs for effective management.
Adenocarcinoma, Mucinous ; Breast Neoplasms ; Carcinoma, Signet Ring Cell ; Cell Differentiation ; Drug Therapy ; Epidermal Growth Factor ; Estrogens ; Humans ; Mucins ; Neoadjuvant Therapy ; Polymerase Chain Reaction ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Receptor, ErbB-2 ; Trastuzumab

Squamous cell carcinoma of the breast and its subtype, basal-human epidermal growth factor receptor 2 (HER2) phenotype, are very rare. Herein, we report a patient who developed recurrence of squamous cell carcinoma of the breast with basal-HER2 subtype 6 years after the initial diagnosis of invasive ductal carcinoma of the HER2 subtype. To the best of our knowledge, recurrence of invasive ductal carcinoma in the form of metaplastic squamous cell carcinoma of basal-HER2 subtype has not been reported previously. We present a pathological perspective of our experience.
Breast ; Carcinoma, Ductal ; Carcinoma, Squamous Cell ; Diagnosis ; Epidermal Growth Factor ; Humans ; Pathology ; Phenotype ; Receptor, Epidermal Growth Factor ; Recurrence