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

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

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

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

PURPOSE: We evaluated the clinical value of breast magnetic resonance imaging (MRI) in patients who underwent breast-conserving surgery (BCS). The degree of correlation between pathology size and MRI or ultrasonography (US) size was compared based on breast cancer subtypes. In addition, we investigated the positive margin rates. METHODS: Patients with invasive breast cancer who underwent preoperative breast MRI and US between 2011 and 2016 were included in the study. Lin's concordance correlation coefficient was used to measure the correlation between MRI or US andpathologic tumor extent. Tumor extent was defined as pathologic tumor size, including in situ carcinoma. Margin positivity was assessed based on frozen-section examination. RESULTS: A total of 516 patients with a single tumor who underwent BCS were included in the study. The correlation between pathologic size and MRI was significantly higher than that of US (r = 0.6975 vs. 0.6211, p = 0.001). The superiority of MRI over US in measuring the pathologic extent was only observed in triple-negative breast cancer (TNBC; r = 0.8089 vs. 0.6014, p < 0.001). The agreement between MRI or US and tumor extent was low for the human epidermal growth factor receptor 2 (HER2)-positive subtype (MRI: 0.5243, US: 0.4898). Moreover, the positive margin rate was higher in the HER2-positive subtype than in the others (luminal/HER2-negative: 11.6%, HER2-positive: 23.2%, TNBC: 17.8%, p = 0.019). The post hoc analysis showed that the HER2-positive subtype was more likely to show positive margins than the luminal/HER2-negative subtype (p = 0.007). CONCLUSION: Breast MRI was superior to US in the preoperative assessment of the pathologic extent of tumor size; this was most evident in TNBC. For HER2-positive tumors, imaging-pathologic discordance resulted in higher positive margin rates than that with other subtypes.
Breast Neoplasms ; Breast ; Humans ; Magnetic Resonance Imaging ; Mastectomy, Segmental ; Pathology ; Receptor, Epidermal Growth Factor ; Receptor, ErbB-2 ; Triple Negative Breast Neoplasms ; Ultrasonography

PURPOSE: There is cumulative evidence that changes in biomarker status occur frequently during the metastatic progression of breast cancer and affect treatment response. The purpose of this study was to evaluate the frequency of biomarker changes in metastatic breast cancer (MBC) and its impact on prognosis. METHODS: A total of 152 patients diagnosed with MBC at the time of initial diagnosis or during post-surgical follow-up were included. Changes in biomarker status in MBCs, their frequency according to various metastatic sites, tumor characteristics, and their association with patient survival were analyzed. RESULTS: Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67 status changed in 9 (6.0%), 40 (26.3%), 12 (7.9%), and 29 (19.1%) patients, respectively. ER, PR, and HER2 mainly showed positive to negative conversion, whereas Ki-67 changed mostly from a low to high index. There were no differences in the frequencies of biomarker changes according to the metastatic sites. As for ER and HER2, cases with negative conversion showed low expression levels in the primary tumor. Survival analyses indicated that a positive to negative conversion of ER was an independent poor prognostic factor in patients with primary ER-positive breast cancer. CONCLUSION: Changes in biomarker status are not rare, and usually occur in an unfavorable direction in breast cancer metastases. Negative conversion of ER status is a predictor of poor prognosis. Thus, it is beneficial to evaluate changes in biomarker status in MBC not only for the purpose of determining treatment options but also for prognostication of patients.
Biomarkers ; Breast Neoplasms ; Breast ; Diagnosis ; Estrogens ; Follow-Up Studies ; Humans ; Neoplasm Metastasis ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone

PURPOSE: Neoadjuvant chemotherapy (NAC) is less effective for luminal breast cancer because luminal breast cancer has a lower rate of pathological complete response (pCR) after NAC than human epidermal growth factor receptor 2 (HER2)-type and triple-negative breast cancer (TNBC). We investigated the efficacy of NAC and the predictive factors of a better response in luminal breast cancer. METHODS: Between 2010 and 2016, we retrieved data of 244 patients with clinically node-positive breast cancer who were treated with NAC followed by surgery from a prospectively collected database. We classified breast cancer into luminal HER2⁻ and non-luminal HER2⁻ breast cancer (luminal HER2⁺, HER2⁺, and TNBC types). We analyzed each subtype with respect to surgical outcomes, response to NAC, and determined variables associated with surgical outcomes and response in patients with luminal HER2⁻ breast cancer. RESULTS: The total, breast, and axillary pCR rates were significantly lower in 114 patients with luminal HER2⁻ breast cancer than in those with other subtypes (7.9%, 12.3%, and 22.8%, respectively). However, breast-conserving surgery (BCS) conversion and tumor response rates did not significantly differ between patients with luminal HER2⁻ and those with non-luminal HER2⁻ breast cancer (p = 0.836 and p = 0.180, respectively). In the multivariate analysis, high tumor response rate (≥ 46.4%) was significantly associated with an increased BCS conversion rate. In the subgroup analysis of luminal HER2⁻ breast cancer, the multivariate analysis showed that higher Ki67 expression and axilla pCR and BCS conversion rates were significantly associated with tumor response to NAC. CONCLUSION: Despite the low pCR rate, the tumor response and BCS conversion rates after NAC of luminal HER2⁻ breast cancer were similar to those of other subtypes. NAC has the potential benefit of reducing the size of breast cancer, thereby increasing the BCS conversion rate in luminal HER2⁻ breast cancer.
Axilla ; Breast Neoplasms ; Breast ; Drug Therapy ; Humans ; Mastectomy, Segmental ; Multivariate Analysis ; Neoadjuvant Therapy ; Phenobarbital ; Polymerase Chain Reaction ; Prospective Studies ; Receptor, Epidermal Growth Factor ; Triple Negative Breast Neoplasms

PURPOSE: Although the effect of lysosome-associated protein transmembrane 4 beta (LAPTM4B) on the proliferation, migration, and invasion of breast cancer (BC) cells has already been studied, its specific role in BC progression is still elusive. Here, we evaluated the effect of different levels of LAPTM4B expression on the proliferation, invasion, adhesion, and tumor formation abilities of BC cells in vitro, as well as on breast tumor progression in vivo. METHODS: We investigated the influence of LAPTM4B expression on MCF-7 cell proliferation, invasion, adhesion, and tube formation abilities in vitro through its overexpression or knockdown and on breast tumor progression in vivo. RESULTS: Cell growth curves and colony formation assays showed that LAPTM4B promoted the proliferation of breast tumor cells. Cell cycle analysis results revealed that LAPTM4B promoted the entry of cells from the G1 into the S phase. Transwell invasion and cell extracellular matrix adhesion assays showed that LAPTM4B overexpression increased the invasion and adhesion capabilities of MCF-7 cells. More branches were observed in MCF-7 cells overexpressing LAPTM4B under an electron microscope. In comparison with LAPTM4B overexpression, LAPTM4B knockdown decreased the expression of vascular endothelial growth factor-A and significantly inhibited the vasculogenic tube formation ability of tumors. These results were also verified with western blot analysis. CONCLUSION: LAPTM4B promoted the proliferation of MCF-7 cells through the downregulation of p21 (WAF1/CIP1) and caspase-3, and induced cell invasion, adhesion, and angiogenesis through the upregulation of hypoxia-inducible factor 1 alpha, matrix metalloproteinase 2 (MMP2), and MMP9 expression. This specific role deems LAPTM4B as a potential therapeutic target for BC treatment.
Blotting, Western ; Breast Neoplasms ; Breast ; Caspase 3 ; Cell Cycle ; Disease Progression ; Down-Regulation ; Extracellular Matrix ; Hypoxia-Inducible Factor 1 ; In Vitro Techniques ; Matrix Metalloproteinase 2 ; MCF-7 Cells ; S Phase ; Up-Regulation ; Vascular Endothelial Growth Factor A

Breast cancer (BC) is still the most common cancer among women worldwide. Amongst the subtypes of BC, triple negative breast cancer (TNBC) is characterized by deficient expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. These patients are therefore not given the option of targeted therapy and have worse prognosis as a result. Consequently, much research has been devoted to identifying specific molecular targets that can be utilized for targeted cancer therapy, thereby limiting the progression and metastasis of this invasive tumor, and improving patient outcomes. In this review, we have focused on the molecular targets in TNBC, categorizing these into targets within the immune system such as immune checkpoint modulators, intra-nuclear targets, intracellular targets, and cell surface targets. The aim of this review is to introduce and summarize the known targets and drugs under investigation in phase II or III clinical trials, while introducing additional possible targets for future drug development. This review brings a tangible benefit to cancer researchers who seek a comprehensive comparison of TNBC treatment options.
Breast Neoplasms ; Drug Therapy ; Estrogens ; Female ; Humans ; Immune System ; Neoplasm Metastasis ; Progesterone ; Prognosis ; Receptor, Epidermal Growth Factor ; Triple Negative Breast Neoplasms