Clinical characteristics and clinicopathological correlations of bilateral breast cancer in China: A multicenter study from Chinese Society of Breast Surgery (CSBrS-006).

OBJECTIVE: To investigate the clinical characteristics and clinicopathological correlations of bilateral breast cancer (BBC) in China. METHODS: Data of 440 patients diagnosed with BBC in 2018 were collected from 33 centers of the Chinese Society of Breast Surgery. Demographic characteristics, bilateral tumor characteristics, and comprehensive treatment data were obtained. Correlations between the clinicopathological characteristics of bilateral tumors were analyzed. RESULTS: The proportion of BBC was 0.22%-3.08%. A total of 33 (7.5%) patients had a family history of malignant tumors, 304 (69.1%) patients had synchronous BBC. Only 1 (0.2%) patient was male. More than half of all patients received concurrent or asynchronous endocrine/chemotherapy, 32.5% of all human epidermal growth factor receptor 2 (HER2)-positive patients received HER2-targeted therapy, and approximately 21.6% of all patients received radiotherapy. The most common pathological cancer type was invasive ductal cancer (>60%). Approximately 70% of all patients had bilateral hormone receptor (HR)-positive tumors and presented with a single breast mass. Significant correlations were found with pathological type, histological grade, locations of tumor, molecular subtype, Ki-67 index, tumor site and size of bilateral tumors. Results of the subgroup analysis showed more clinicopathological characteristics when synchronous BBC was compared with metachronous BBC. CONCLUSIONS: In China, the clinicopathological characteristics of bilateral tumors showed significant correlations, and more significant clinicopathological correlations were observed when synchronous BBC was compared with metachronous BBC.

FSIP1 is correlated with estrogen receptor status and poor prognosis.

Fibrous sheath interacting protein 1 (FSIP1) is frequently activated in a variety of tumors including breast cancer. However, the clinical significance of FSIP1 in hormone receptor (HR)-positive breast cancer is unclear. We analyzed the expression and clinical significance of FSIP1 in human breast cancer databases. A comprehensive analysis of 1094 gene expression profiles of breast cancer in The Cancer Genome Atlas revealed that FSIP1 overexpression correlated with decreased overall survival in HR-positive breast cancer patients. We also showed that knockdown of FSIP1 in T47D and BT474 cell lines resulted in decreased cell proliferation and migration in vitro. Furthermore, we retrospectively examined the expression and prognostic value of FSIP1 in 129 breast cancer patients to examine the expression of FSIP1 by the immunohistochemical method and got the similar results that high expression of FSIP1 predicts poor prognosis. Therefore, FSIP1 has a crucial role in HR-positive breast cancer and represents an attractive therapeutic target for HR-positive breast cancer.

Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model.

BACKGROUND: Papillary carcinoma is an uncommon type of breast cancer. Additionally, patients with huge breast papillary carcinoma are extremely rare in clinical practice. To improve therapeutic effect on such patients, it is urgent to explore biologically and clinically relevant models of the disease to discover effective drugs. METHODS: We collected surgical tumor specimens from a 63-year-old Chinese woman who has been diagnosed breast papillary carcinoma. The tumor was more than 15 cm in diameter, and applied to establish patient-derived papillary carcinoma organoids that could continuously propagate for more than 6 months. RESULTS: The papillary carcinoma organoids matched the histological characteristics of orginal tumor by H&E staining identification, and maintained the expression of the breast cancer biomarkers by IHC, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2) and antigen Ki-67 (Ki67). In addition, we performed a 3-D drug screening to examine the effects of endocrine drugs (Fulvestrant, Tamoxifen) and targeted therapy drugs (Palbociclib, Everolimus, BKM120) on breast papillary carcinoma in the mimic in vivo environment. The drug sensitivities of our breast papillary carcinoma organoids were investigated as follows, Fulvestrant (IC50 0.275 µmol), Palbociclib (IC50 2.21 µmol), BKM120 (IC50 3.81 µmol), Everolimus (IC50 4.45 µmol), Tamoxifen (IC50 19.13 µmol). CONCLUSIONS: These results showed that an effective organoid platform for 3-D in vitro culture of breast cancer organoids from patients with breast papillary carcinoma could be used to identify possible treatments, and might be commonly applied to explore clinicopathological characteristics of breast papillary carcinoma.

Establishment and characterization of breast cancer organoids from a patient with mammary Paget's disease.

BACKGROUND: Mammary Paget's disease (MPD) is an uncommon cutaneous intraepithelial malignancy with ulceration of the nipple or areola. Its pathogenesis and genomic mutation remain largely unknown and no cell lines are established from primary tumors. METHODS: We collected surgical tumor specimens from a 65-year-old Chinese woman diagnosed with MPD and established patient-derived breast cancer (BC) organoids from MPD using organoid culture technology. RESULTS: We successfully propagated BC organoids from a patient with MPD for more than 6 months. The organoids were cultured for long-term expansion without any change in spherical organoid morphology. Besides, the spherical organoid morphology did not change when they underwent cryopreservation after resuscitation. The H&E staining and immunohistochemistry analyses showed the similar morphological and histological features of the organoids compared with their paired original BC tissues. The organoids retained positive expression of breast cancer biomarkers: estrogen receptor, progesterone receptor, antigen Ki-67 and negative expression of human epidermal growth factor receptor 2. We also showed that MPD organoids recapitulated the unique genomic landscape including copy number alterations, mutational load, mutational signatures and cancer gene mutations by whole genome sequencing. In situ senescence-associated acid beta galactosidase assay confirmed senescence phenomenon existed in the process of organoids culture and there was no significant difference in the proportion of senescent organoids after organoid passage and resuscitation. CONCLUSIONS: Our results suggested that an effective platform for ex vivo BC organoids from MPD patients could be used to explore clinicopathological and genomic characteristics of these patients.

Characterization of ascites-derived tumor cells from an endometrial cancer patient.

Improved treatment outcomes for the endometrial cancer patient requires precision methods to investigate the biology of this disease and clinically relevant models to test treatment drugs. Hence, we applied a personalized platform to investigate whether in vitro and in vivo models could accurately predict effective treatment regimens. We successfully expanded ascites-derived tumor cells from an endometrial cancer patient with malignant ascites using ascites collected prior to chemotherapy treatment. Hematoxylin-eosin and immunohistochemistry staining of ascites-derived tumor cells confirmed the source of endometrial cancer cells. Ascites-derived tumor cells were sensitive to cisplatin and doxorubicin single-agent treatments in CCK-8 assay and 3-D culture, a condition that more closely mimics the in vivo environment. We further showed that ascites-derived tumor cells from this patient could form tumors in NOD/SCID mice with preserved morphological characteristics. A remarkable concordance between the clinical response of cisplatin and the results of in vitro and in vivo drug tests reflected the reliability of our personalized approach in this case. Together, our results indicated that an effective platform for ex vivo and in vivo culture of ascites-derived tumor cells from our endometrial cancer patient could be applied to identify treatment options, and may be commonly used in treating cancer patients with malignant ascites in the future.

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer.

BACKGROUND/AIMS: Previous preclinical and clinical studies have reported a positive correlation between the expression of the C-C chemokine receptor 7 (CCR7) and the incidence of lymph node metastasis in breast cancer. However, the prognostic relevance of CCR7 expression in breast cancer remains contradictory till now. The aim of this study is to assess the correlation of the CCR7 expression with other clinicopathological features and prognosis in breast cancer. METHODS: The CCR7 gene amplification and mRNA expression levels from approximately 3,000 patients were retrieved from human breast cancer databases and analyzed. Furthermore, a total of 188 primary triple negative breast cancer patients were enrolled in this study (diagnosed since January 2009 to January 2013 from the Second Hospital of Dalian Medical University). The protein levels of CCR7 were examined by immunohistochemistry using paraffin-embedded tumor tissues. RESULTS: The analysis of gene amplification and mRNA levels showed the expression of CCR7 in breast cancer correlated with better prognosis. When we compared the CCR7 expressions in different subtypes, the basal-like group showed the highest expression of CCR7 and exhibited a better prognosis. Consistently, Kaplan-Meier analysis of 188 triple negative breast cancer patients showed that the prognosis of patients with positive CCR7 expression was significantly better than those with negative expression (HR=0.642, p=0.0275). Additionally, we also observed a positive correlation between lymph node metastasis and the CCR7 expression (p=0.0096). CONCLUSIONS: Our results indicated that elevated CCR7 expression as a marker for increased lymph node metastasis, in addition to serve as an independent prognostic indicator for better overall survival in triple negative breast cancer patients.

Nestin positively regulates the Wnt/ß-catenin pathway and the proliferation, survival and invasiveness of breast cancer stem cells.

INTRODUCTION: We investigated Nestin expression in triple-negative breast cancer and examined how the modulation of Nestin expression affects cell cycle progression, survival, invasion and regulatory signaling in breast cancer stem cells (CSC) in vitro. METHODS: Nestin expression in 150 triple-negative breast cancer specimens were examined by immunohistochemistry. The role of Nestin expression in tumorigenesis was examined by assaying naturally occurring Nestinhigh/Nestinlow CSC from 12 breast cancer tissues, as well as CSC from 26 clinical specimens, where Nestin overexpression and silencing was achieved by genetic manipulation, for their ability to form mammospheres and induce solid tumors. Cell cycle progression, spontaneous apoptosis and invasiveness of Nestin-silenced breast CSC were investigated by flow cytometry and transwell assays. The relative levels of expression of epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin pathway-related molecules were determined by western blotting. RESULTS: Nestin expression was significantly associated with poor survival in patients with triple-negative breast cancer (P = 0.01). Nestinhigh breast CSC rapidly formed typical mammospheres in vitro. Nestinhigh, but not Nestinlow CSC, efficiently formed solid tumors in vivo. Nestin silencing induced cell cycle arrest at G2/M (52.03% versus 19.99% in controls) and promoted apoptosis (36.45% versus 8.29% in controls). Nestin silencing also inhibited breast CSC invasiveness, and was associated with significantly upregulated E-cadherin, while N-cadherin, vimentin, a-smooth muscle actin (a-SMA), matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF) expression was downregulated (P <0.05 for all). Nestin silencing also upregulated Axin, glycogen synthase kinase-3 beta (GSK-3ß), adenomatous polyposis coli (APC), and peroxisome proliferator-activated receptor alpha (PPARa), and downregulated ß-catenin, c-Myc, cyclin D and MMP-7 expression in CSC. Inhibition of the Wnt/ß-catenin pathway mitigated mammosphere formation in Nestinhigh CSC, while inhibition of GSK-3ß promoted the mammosphere formation in Nestinlow CSC (P <0.05 for all). CONCLUSIONS: Our data indicates that Nestin positively regulates the proliferation, survival and invasiveness of breast CSC by enhancing Wnt/ß-catenin activation.

ARID1A: a potential prognostic factor for breast cancer.

The aim of this study is to explore the expression of BAF250a protein in breast cancer and its association with the clinical and pathological characteristics and prognosis of breast cancer. The expression status of BAF250a protein was detected by Western blot analysis and immunohistochemical staining. The relationship between BAF250a proteins and clinicopathological parameters in 496 breast cancer specimens was analyzed. Western blot analysis showed that BAF250a protein had a lower expression in breast cancer specimens than in matched normal breast tissue (104.38 ± 11.65 vs. 55.94 ± 10.27; P = 0.004, t test). Among the 496 enrolled breast cancer patients, BAF250a protein expression was absent in 324 (65.3 %). Universal and multiple analyses indicated that BAF250a protein expression loss was significantly related to histological grade, metastatic nodes, tumor node metastasis (TNM) stage, and the expression of estrogen receptor (ER), progesterone receptor (PR), c-erbB-2, and p53 (all P < 0.05). For TNM stage, rank correlation coefficients were 0.199 and 0.191, respectively, (P < 0.05), but BAF250a protein deletion had either a positive or a negative correlation with ER, PR, c-erbB-2, and p53 protein expression (correlation coefficients were 0.231, 0.207, -0.098, -0.128; P < 0.05). Analysis of survival rates showed that the patients with BAF250a protein expression attained a significantly better postoperative disease-specific survival than those with BAF250a protein deletion (88.4 vs. 79.0%; P = 0.003). In the Cox regression test, BAF250a protein deletion was detected as an independent prognostic factor (P = 0.014). BAF250a protein might be a new potential target for breast cancer treatment.

EphB4 regulates the growth and migration of pancreatic cancer cells.

Pancreatic cancer is a serious threat to human life. Moreover, its treatment is complicated and its prognosis is very poor. Therefore, a new method for the diagnosis and treatment of pancreatic cancer is very essential. In this study, a eukaryotic expression plasmid targeting EphB4 was constructed and transfected into PANC-1 pancreatic cancer cells to investigate the inhibition of cell growth and the progression of iRNA against EphB4. This study provides the basis for the gene therapy of pancreatic cancer. The recombinant eukaryotic EphB4 expression plasmid, pSIREN-RetroQ-ZsGreen-EphB4 and a negative control plasmid, pSIREN-RetroQ-ZsGreen-N, were constructed. At 48 h after transfection, the relative messenger RNA (mRNA) and protein levels of EphB4 were measured by RT-PCR and western blot. The proliferation of the transfected cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while cell migration ability was analyzed using the scratch migration assay. At 48 h after transient transfection, EphB4 mRNA expression was significantly decreased in transfected PANC-1 cells as compared to the control group (P < 0.01). In vitro, inhibition of EphB4 expression weakened the proliferation and cell migration ability of PANC-1 cells compared to the control group. The small interfering RNA (siRNA) eukaryotic expression plasmid vector targeting EphB4 was successfully constructed and effectively transfected into PANC-1 cells. The recombinant plasmid can inhibit the expression of EphB4 mRNA and protein in PANC-1 cells, as well as cell growth and migration.

Clinical implications of GRHL3 protein expression in breast cancer.

The objective of this study was to investigate the expression and significance of the GRHL3 protein in breast cancer diagnosis and prognosis. Overall, 111 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. The GRHL3 protein expression status in the breast cancers was evaluated by immunohistochemistry. The relationship between GRHL3 protein expression status and clinicopathological factors and the breast cancer prognoses was also determined. In total, 71 (63.96%) out of 111 cases were found to express GRHL3 protein. GRHL3 expression was higher in breast cancers, compared to other pathologic cancer types (χ (2) = 5.68, P < 0.05). Moreover, GRHL3 protein was also observed to correlate with breast cancer clinical stage and histological grade (χ (2) = 7.99, P < 0.05 and χ (2) = 7.907, P < 0.05, respectively). Interestingly, triple-negative breast cancers had lower expression rates than other breast cancers (41.18 vs. 71.28%, P < 0.05). GRHL3 was shown to be an independent prognostic factor of breast cancer in Cox regression analysis. Altogether, our results indicate predominant GRHL3 expression in breast cancers, especially non-triple-negative cancers and early stage cancers. GRHL3 expression appeared to decrease with tumor progression. Survival analysis demonstrated the inhibitory effect of GRHL3 in breast cancer. These results strongly suggest the possible involvement of GRHL3 in tumor suppression.

Clinical implications of SPRR1A expression in diffuse large B-cell lymphomas: a prospective, observational study.

BACKGROUND: Certain markers have been identified over the last 10 years that facilitate the prediction of a patient's prognosis; these markers have been proposed to be useful for risk stratification of lymphoma patients and for the development of specific therapeutic strategies. In the present study, we assessed the potential prognostic value of SPRR1A expression in 967 patients with diffuse large B-cell lymphomas. METHODS: All patients were enrolled between 2001 and 2007 (median follow-up, 53.3 months) in the Second Hospital of Dalian Medical University, First Hospital of China Medical University, and Liaoning Cancer Hospital. Immunohistochemical analysis was used to evaluate the expression of SPRR1A. Survival was analyzed using the Kaplan-Meier method. Multivariate analysis was conducted to adjust the effect of SPRR1A expression for potential, well-known, independent prognostic factors. RESULTS: Of the 967 patients examined, SPRR1A expression was detected in 305 (31.54%) patients on immunohistochemical analysis. The 5-year survival rate was significantly lower in patients with SPRR1A expression than in those without (26.9% vs. 53.2%, P < 0.001). Multivariate analysis identified SPRR1A expression as an independent predictor of survival in addition to lactate dehydrogenase level, clinical stage, and histologic subtype. CONCLUSIONS: SPRR1A expression may be useful as a prognostic factor for diffuse large B-cell lymphoma.

PARP Inhibitor for Neoadjuvant Therapy in HER2-Negative Breast Cancer: A Systematic Review and Meta-Analysis of Efficacy and Safety.

Poly-ADP ribose polymerase inhibitor (PARPi) is approved for HER2-negative advanced breast cancer with BRCA1/2 mutation. In recent years, many studies have explored the application of PARPi in neoadjuvant therapy, but failed to reach a unified conclusion. PubMed, Clinicaltrials.gov, Cochrane CENTRAL, Embase, and key oncological meetings for trials were searched for studies reporting neoadjuvant regimens with PARPi in HER2-negative breast cancer. Pathological complete response (pCR), residual cancer burden (RCB), breast-conservation surgery rate (BCSR), clinical response, and adverse events were extracted and pooled in a meta-analysis using the Mantel Haenszel random/fixed effects model. Subgroup analyses of pCR were conducted according to BRCA1/2 status, and hormone receptor (HR) status. Five studies (N = 1223) were included, the addition of PARPi to neoadjuvant regimens significantly increased pCR rates (HR 1.45, 95%CI 1.09-1.92, P = .01, I2 = 86%). In subgroup analysis, the addition of PARPi increased the pCR rate both in HR-positive (n = 383) and HR-negative (n = 431) subgroups, which showed a dominant effect of PARPi regardless of HR status (HR 2.07, 95%CI 1.33-3.23, P = .001, I2 = 0%; HR 1.85, 95%CI 1.39-2.26, P < .0001, I2 = 0%, respectively). However, when we performed a subgroup analysis based on the status of BRCA1/2, no further benefit for PARPi was found. Adverse reactions were generally tolerable. Other outcome indexes, including RCB, clinical response, BCSR, and PARPi did not show a clinical benefit. Regardless of BRCA1/2 status, PARPi in neoadjuvant therapy, can improve the pCR rate of HER2-negative breast cancer, especially in HR-positive patients. Thus, we should have performed larger randomized trials and provided a stronger evidence-based basis.

STIL facilitates the development and malignant progression of triple-negative breast cancer through activation of Fanconi anemia pathway via interacting with KLF16.

BACKGROUND: STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear. METHODS: We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed. RESULTS: Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2. CONCLUSIONS: Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.

Comprehensive review of solid tumor bone marrow metastasis.

Bone marrow metastasis (BMM) of solid tumors refers to a group of diseases that originate from non-hematopoietic malignant tumor cells invading the bone marrow (BM) through complex metastatic patterns. If BMM identification is delayed, the disease will rapidly develop into disseminated carcinogenesis of the BM, which manifests as a series of hematological disorders and microangiopathic hemolytic anemia, leading to serious life-threatening conditions. Although the study of solid tumor BMM is receiving increasing attention, study remains limited, and most descriptions are derived from case reports. Currently, clinicians have insufficient understanding of BMM, and BMM occurrence is often not recognized early or treated effectively, resulting in high mortality rates. In this article, we review the epidemiology, molecular mechanisms, clinical diagnosis, treatment, and prognosis of solid tumor BMM.

mTOR inhibitor introduce disitamab vedotin (RC48-ADC) rechallenge microtubule-chemotherapy resistance in HER2-low MBC patients with PI3K mutation.

This study aimed to explore the efficacy and potential mechanisms of rechallenge therapy with microtubule-targeting agents (MTAs) in patients with HER2-low metastatic breast cancer (MBC). We performed a systematic review to investigate the rechallenge treatment concept in the field of HER2-low MBC treatment and utilized a series of cases identified in the literature to illustrate the concept. Here we reported two clinical cases of HER2-low MBC patients whose disease progressed after prior treatment with MTAs such as docetaxel and vincristine. When rechallenged with disitamab vedotin ((RC48-antibody-drug conjugate (ADC), a monomethyl auristatin (MMAE) MTA)), both patients achieved a partial response and the final progression-free survival (PFS) was 13.5 and 9 months, respectively. Genomic profiling detected a PIK3CA H1047R mutation in the patients. The patients were treated with everolimus before being rechallenged with RC48, which may lead to a better response. This study further summarizes and analyzes the potential mechanism of the PI3K-AKT signaling pathway in MTA resistance and reveals that the PIK3CA H1047R mutation may be a potential molecular marker for the efficacy prediction of mTOR inhibitors, providing new insights and potential therapeutic strategies for the application of MTAs to MBC patients.

Axillary lymph node dissection in triple-negative or HER2-positive breast cancer patients with clinical N2 achieving pathological complete response after neoadjuvant therapy: Is it necessary?

AIM: This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）. BACKGROUND: Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery. METHODS: A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined. RESULTS: Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1-19.1), compared to those who did achieve breast pCR, P < 0.001. CONCLUSION: For cN2 TN or HER2+ breast cancer patients who achieve breast pCR following NAT, consideration could be given to downstaging and performing an axillary SLNB or TAD.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

Purpose: This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. Methods: The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. Results: In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. Conclusion: We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

Clinical implications of EphB4 receptor expression in pancreatic cancer.

In the study, we investigated the correlation between EphB4 receptor expression and the angiogenesis of pancreatic cancer. EphB4 receptor is unevenly distributed or distributed with small patches in pancreatic ductal cell cancer. While EphB4 receptor was not expressed in normal pancreatic tissues. It can be observed that the mRNA of EphB4 receptor is high expressed in all 15 cases of pancreatic ductal cell cancer tissues but not expressed in normal pancreatic tissues. Finally, positive correlation was observed between the mRNA expression level of EphB4 receptor and MVD. Immunohistochemical analysis showed that EphB4 receptor protein expression was related to tumor differentiation and clinical stage. It can be observed that MVD is relevant to histological differentiation and clinical stage. EphB4 receptor is correlated to the initiation, progression and tumor angiogenesis. In conclusion, EphB4 receptor maybe a promising targeted goal of antiangiogenic formation, which provides a new approach and method for tumor treatment.

Efficacy analysis of neoadjuvant chemotherapy with or without anthracyclines in female patients with HER2-positive breast cancer in China: a nationwide, multicenter, 10-year retrospective study (CSBrS-012).

Background: In the era of targeted therapy, whether patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are exempted from anthracycline usage in the neoadjuvant setting is controversial. Objectives: Our objective was to retrospectively analyze the differences in pathological complete remission (pCR) rates between the anthracycline group and the nonanthracycline group. Design: The CSBrS-012 study (2010-2020) included female primary breast cancer patients with neoadjuvant chemotherapy (NAC) who underwent standard breast and axillary surgery post-NAC. Methods: A logistic proportional hazard model was applied to estimate the association of covariates with pCR. Propensity score matching (PSM) was performed to balance the differences in baseline characteristics, and subgroup analyses were performed using the Cochran-Mantel-Haenszel test. Results: A total of 2507 patients were enrolled: the anthracycline group (n = 1581, 63%) and the nonanthracycline group (n = 926, 37%). A pCR was recorded in 17.1% (271/1581) of patients in the anthracycline group and in 29.3% (271/926) in the nonanthracycline group, and the difference in the pCR rate between the two groups was statistically significant [odds ratio (OR) = 2.00, 95% confidence interval (CI) (1.65-2.43); p < 0.001). In the subsequent subgroup analysis, substantial differences in pCR rates between the anthracycline and nonanthracycline groups were detected in the nontargeted [OR = 1.91, 95% CI (1.13-3.23); p = 0.015] and dual-HER2-targeted populations [OR = 0.55, 95% CI (0.33-0.92); p = 0.021) before PSM, whereas differences vanished after PSM. The pCR rates between the anthracycline and nonanthracycline groups did not differ for the single target population, either before or after PSM. Conclusion: In the presence of trastuzumab and/or pertuzumab, the pCR rate of patients with HER2-positive breast cancer receiving anthracycline was not superior to that of patients receiving nonanthracycline. Thus, our study further provides clinical evidence for exempting anthracycline treatment in HER2-positive breast cancer in the era of targeted therapy.

Nomogram for predicting axillary upstaging in clinical node-negative breast cancer patients receiving neoadjuvant chemotherapy.

PURPOSE: The prediction of axillary lymph node status after neoadjuvant chemotherapy (NAC) becoming critical because of the advocation of the de-escalation of axillary management. We investigate associated factors of axillary upstaging in clinical node-negative (cN0) breast cancer patients receiving NAC to develop and validate an accurate prediction nomogram. METHODS: We retrospectively analyzed 1892 breast cancer patients with stage of cT1-3N0 treated by NAC and subsequent surgery between 2010 and 2020 in twenty hospitals across China. Patients randomly divided into a training set and validation set (3:1). Univariate and multivariate logistic regression analysis were performed, after which a nomogram was constructed and validated. RESULTS: In total, pathologic node negativity (ypN0) achieved in 1406 (74.3%) patients and another 486 (25.7%) patients upstaged to pathologic node positive (ypN+). Breast pathologic complete response (bpCR) was achieved in 445 (23.5%) patients and non-bpCR in 1447 (76.5%) patients. A nomogram was established by ER, tumor histology, HER2 status, cycle of NAC treatment, and the bpCR, which were confirmed by multivariate logistic analysis as independent predictors of nodal upstaging in the training cohort (n = 1419). The area under the receiver operating characteristic curve (AUC) of the training cohort and validation cohort (n = 473) were 0.73 (95% CI 0.693-0.751) and 0.77 (95% CI 0.723-0.812) respectively. CONCLUSION: We present a nomogram with a nationwide large sample data which can effectively predict axillary upstaging after neoadjuvant chemotherapy to give better advice for individualized axillary lymph node management of breast cancer.