Objective To investigate the regulatory effects of bombesin on the growth of human immortalized gastric epithelial cell line(GES-1), and its mechanisms. Methods ① The expression of gastrin releasing peptide receptor(GRP-R) mRNA in GES-1 was detected. ② The expression of GRP-R protein was tested by cross-linking experiment and the location of the receptors in the cells were investigated by cytochemistry. ③GES-1 cell line was incubated with varying concentrations of bombesin with or without its antagonist and growth of the cell line was determined. ④The effect of protein kinase C (PKC) inhibitor on cell growth induced by bombesin was studied. ⑤After treated with bombesin, the intracellular IP 3 and translocation of PKC activity were measured in GES-1. ⑥Semiquantification of GRP-R mRNA in this cell line treated with bombesin was performed. Results ①Expression of mRNA of GRP-R was demonstrated in GES-1 cells. ②The GRP-R protein was about 75?103 as revealed by cross-linking study, and the receptors were identified on the cell membranes by cytochemistry. ③Bombesin stimulated the growth of GES-1 significantly, which could be inhibited by specific antagonist of bombesin. ④Bombesin-induced growth of GES-1 was also inhibited by PKC inhibitor. ⑤Bombesin induced an increase of IP 3 generation in GES-1 as well as remarkable translocation of PKC activity from cytoplasm to the cell membranes. ⑥An increase in GRP-R mRNA was induced by treatment of cell line with bombesin. Conclusions Bombesin stimulates the growth of this GES-1 via its receptor GRP-R and through IP 3, PKC signal pathway. The increase in expression of GRP-R mRNA in GES-1 induced by bombesin indicates that bombesin might upregulate the GRP-R in the GES-1 cells.

BACKGROUND: Pertuzumab has been approved for application in China by the National Medical Products Administration, and both national and international guidelines make recommendations for the use of neoadjuvant treatment with trastuzumab or trastuzumab + pertuzumab plus chemotherapy regimens for patients with indications. The goal of this study was to investigate the short-term clinical efficacy of the neoadjuvant therapies trastuzumab and trastuzumab+pertuzumab for patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer in China. METHODS: A real-world study was conducted using the clinicopathological data of patients with early HER2-positive breast cancer who were admitted to the member hospitals of the Chinese Society of Breast Surgery, Chinese Surgical Society of Chinese Medical Association between March 2019 and December 2020. This study analyzed the efficacy and tolerance of trastuzumab+chemotherapy and trastuzumab+pertuzumab+chemotherapy in patients with early HER2-positive breast cancer. The Response Evaluation Criteria in Solid Tumors 1.1 was adopted to evaluate clinical efficacy. The pathological efficacy was evaluated using the MillerPayne grade. The Common Terminology Criteria for Adverse Events (version 5.0) was adopted to evaluate adverse events (AEs). The propensity scores were subjected to propensity score matching using the R language (1:1 matching with a maximum allowable difference of 0.05 between the two groups). Efficacy was compared using the chi-square test, and correlation analysis was performed using linear regression. RESULTS: A total of 1032 patients with early HER2-positive breast cancer met the enrollment criteria and were included in this study. Among these patients, 472 received neoadjuvant trastuzumab+chemotherapy (the trastuzumab group), and 560 received neoadjuvant trastuzumab+pertuzumab+chemotherapy (the trastuzumab+pertuzumab group). The overall pathologic complete response (pCR) rate was 47.2% (487/1032), while the pCR rates of the trastuzumab and trastuzumab+pertuzumab groups were 34.5% (163/472) and 57.9% (324/560), respectively, and the difference was significant (P < 0.001). The incidence of grade 4 AEs was 24/321 (7.5%) in the trastuzumab+pertuzumab group, and there were no cases in which the left ventricular ejection fraction decreased by more than 10%. CONCLUSIONS Patients in the trastuzumab+pertuzumab group had a higher pCR rate than those in the trastuzumab group, and the toxic side effects were tolerable.
Humans ; Female ; Breast Neoplasms/metabolism* ; Neoadjuvant Therapy ; Stroke Volume ; Ventricular Function, Left ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To discuss the androgen receptor (AR) expresion and its association with clinicopathological features and prognosis in early stage triple-negative breast cancer patients (TNBC). Methods: The present study retrospectively analyzed the clinic data of 1 018 patients with early-stage invasive breast cancer treated at the Breast Disease Center at Peking University First Hospital between January 2014 and December 2016, including 1 011 females and 7 males; the age range was 21 to 92 years, and the median age was 57 years. Patients with TNBC were enrolled, and divided into AR positive group and AR negative group according to the expression of AR.The clinicopathological features were analysed, including menopause status, pathological type, T staging, lymph node involvement, anatomic staging, prognostic staging, Ki-67 index, histological grade, vascular tumor thrombus and neuroinvation, and the correlation between the expression of AR and clinicopathological features, curative effect of neoadjuvant chemotherapy and prognosis were calculated. The Student’s t test was used to compare continuous data, the Pearson χ² test or Fisher exact test was used to compare categorical variables, and the Mann-Whitney U test was used for quantitative data. The Kaplan-Meier method was used to analyze survival status, and comparisons between groups were calculated by the log-rank test. Results: This study included 148 TNBC, accounting for 14.5% of all patients, in which all patients were females, and the median age was 55 years, ranging from 27 years to 75 years. The number of AR-positive TNBC was 59, accounted for 39.9% of all TNBC patients, and the numbers of AR-negative were 89, accounted for 60.1%. Ki-67 index, histological grade and prognostic stage were significantly different in AR-positive and AR-negative TNBC(P<0.05). There was no statistically significant difference between AR-positive TNBC and AR-negative TNBC in OS (98.3% vs 95.4%, P=0.830) or in DFS (91.4% vs 91.0%, P=0.812). Among TNBC who received neoadjuvant chemotherapy, AR-positive patients showed a lower pCR rate than AR-negative patients(χ²=4.381, P=0.046). Conclusions AR expression is associated with lower respond to neoadjuvant chemotherapy in TNBC. However, the association between AR expression and prognosis in TNBCs was still not clear.

Objective:To explore the feasibility of classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study included consecutive invasive breast carcinoma pathological diagnosed by core needle biopsy or surgery from January 2013 to December 2013 and carcinoma in situ of breast diagnosed by surgery from January 2013 to December 2015 in Peking University First Hospital. All patients had pretreatment breast MRI images. A total of 251 cases (251 lesions) were included, with 208 invasive breast carcinoma and 43 carcinoma in situ of breast. They were all females and median age was 53 (23-82) years old. Patients were randomly divided into the training ( n=176) and testing dataset ( n=75) in a 7∶3 ratio. In the training dataset, combined with DCE mask and early enhancement images, intratumoral and peritumoral area were semi-automatic segmentation, and radiomics features were extracted and dimension reduction, finally a prediction model was established. Model performance was tested in the testing dataset. Receiver operating characteristic (ROC) curve and area under curve (AUC) were used to analyze the model prediction performance. Results:The prediction models established by intratumoral, peritumoral and intratumoral combined with peritumoral radiomics had good performance. The AUC of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models in differentiating breast carcinoma in situ and invasive carcinoma were 0.865, 0.896 and 0.922 in the testing dataset, there was no significant difference in pairwise comparisons ( P>0.05). The sensitivity of intratumoral, peritumoral and intratumoral combined with peritumoral radiomics prediction models were 77.4%, 87.1%, 83.9%, the specificity were 92.3%, 84.6%, 100%, and the accuracy were 80.0%, 85.3%, 86.7%. Conclusion:It is potential feasible for classification between carcinoma in situ and invasive carcinoma of breast using intratumoral and peritumoral radiomics based on breast DCE MRI.

Objective To investigate the difference of the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein between primary lesions of breast cancer and its synchronous ipsilateral lymph node metastasis,as well as its clinical implications.Methods Retrospectively analyze invasive breast cancer patients treated in Peking University First Hospital from January 2012 to May 2016.The IHC expressions of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein in both the primary and lymph node metastatic lesions are compared and analyzed statistically.The count data were represented as n(％),and comparsion between groups were evaluated using the McNemar test.Results One hundred and fifty-six patients were included,of which on 2 cases (1.3％),estrogen receptor status of primary lesions is different from that of lymph node metastases(P =0.500);on 10 cases (6.4％),progesterone receptor status of primary lesions is different from that of lymph node metastases (P =0.344);on 28 cases (18.0％),Ki-67 protein status of primary lesions is different from that of lymph node metastases (P =0.000 18);on 3 cases (1.9％),human epidermal growth factor receptor 2 status of primary lesions is different from that of lymph node metastases (P =1.000).Conclusion There may be difference between primary lesions and lymph node metastases in the expression of estrogen receptor,progesterone receptor,human epidermal growth factor receptor 2 and Ki-67 protein,which can provide a reference for individualized treatment of breast cancer patients.

Objective:To explore the feasibility of predicting axillary lymph node metastasis of breast cancer using radiomics analysis based on dynamic contrast-enhanced (DCE) MRI.Methods:The retrospective study enrolled 163 patients (163 lesions) with breast cancer diagnosed by core needle biopsy from January 2013 to December 2013 in Peking University First Hospital. The status of axillary lymph nodes in all patients was pathologically confirmed, and they had complete preoperative breast MRI images. Among the 163 patients, 94 patients were confirmed with axillary lymph node metastasis, and 69 patients without axillary lymph node metastasis. They were randomly divided into the training dataset ( n=115) and testing dataset ( n=48) in a 7∶3 ratio. The radiomics analysis was performed in the training dataset, including image preprocessing and labeling, radiomics feature extraction, radiomics model establishment and model predictive performance inspection. Model performance was tested in the testing dataset. Receiver operating characteristic curve and area under curve (AUC) was used to analyze the model prediction performance. Results:Of the 1 075 features extracted from the training dataset, principal component analyses (PCA) features 8, 41 and 67 were selected by random forest classifier. The radiomics model including 3 PCA features reached an AUC of 0.956 (95%CI 0.907-0.988), with sensitivity of 91.2%, specificity of 100% and accuracy of 94.8%. In the testing dataset, the radiomics model including 3 PCA features reached an AUC of 0.767 (95%CI 0.652-0.890), with sensitivity of 80.8%, specificity of 72.7% and accuracy of 77.1%.Conclusion:It is feasible to predict axillary lymph node metastasis using radiomics features based on DCE-MRI of breast cancer.

Objective: To investigate the clinical relevance of prognostic staging according to the AJCC Breast Cancer Staging System, Eighth Edition for evaluation of the prognosis of triple-negative breast cancer. Methods: The clinical data of 293 patients with triple-negative breast cancer who were treated at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2014, were retrospectively analyzed. All patients were female, with age of 53(16) years (M(Q_R)). The patients were staged according to the AJCC Breast Cancer Staging System, Eighth Edition. Survival analysis was performed by Kaplan-Meier method and Log-rank test. The role of clinical staging and prognostic staging in prognostic evaluation was investigated. Results: In all, 293 patients with triple-negative invasive breast cancer with complete clinical data and follow-up data were treated over a 7-year period. The follow-up time was 64.5(32.8) months, the 5-year overall survival (OS) rate was 83.9%, and the 5-year disease-free survival (DFS) rate was 84.1%. The results showed that clinical staging and prognostic staging were correlated with the DFS rate and OS rate of patients with triple-negative breast cancer (χ² were 15.395 to 50.084,P=0.00). However, these two staging systems yielded different results. The prognostic stage of 91.8%(269/293) patients was higher than that of the original anatomical stage. There were significant differences in disease-free survival rate (χ²=22.357,P=0.00) and overall survival rate (χ²=50.084, P=0.00) among patients with different clinical stages. There were significant differences in disease-free survival rate (χ²=15.395,P=0.00) and overall survival rate (χ²=29.187,P=0.00)among patients with different prognostic stages. Conclusions The prognostic stage according to the AJCC Breast Cancer Staging System, Eighth Edition complements the clinical stage. It has a good predictive value for the prognosis of triple-negative breast cancer.