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To strengthen the treatment of genitourinary syndrome of menopause in breast cancer patients

Lingquan KONG ; Jiashuo LIU ; Hao LI ; Hongyuan LI ; Guosheng REN ; Kainan WU

Chinese Journal of Endocrine Surgery.2019;13(5):353-356. doi:10.3760/cma.j.issn.1674-6090.2019.05.001

Genitourinary syndrome of menopause (GSM),is a common disease in postmenopausal women.It is reported that the incidence of GSM in breast cancer patients (79％-95％) was higher than that in normal counterparts (more than 50％).GSM significantly reduced the quality of life in breast cancer patients,but was not given enough attention,and most of breast cancer patients with GSM were not diagnosed and treated.In addition,chemotherapy and endocrine therapy for breast cancer may increase the incidence and severity of GSM.Hence,prevention and treatment of GSM should be strengthened in breast cancer patients.

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A single-center retrospective study on influence factors on surgical methods in DCIS patients

Jing SI ; Chenlian QUAN ; Miao MO ; Rong GUO ; Yonghui SU ; Benlong YANG ; Jiajian CHEN ; Zhimin SHAO ; Jiong WU

Chinese Journal of Endocrine Surgery.2019;13(5):357-363. doi:10.3760/cma.j.issn.1674-6090.2019.05.002

Objective To evaluate the influence factors on surgical methods in DCIS (Ductal carcinoma in situ) patients,and the prognosis of different surgical methods in a 10-year single-center retrospective study.Methods We retrospectively included 1557 DCIS patients who received treatments in our center from Jan.2006 to Nov.2016.T tests,Chi-square analysis and logistic regression analysis were used to analyze influence factors on surgical methods.Kaplan-Meier and Log-rank analysis were used to evaluate recurrence-free survival(RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods.Results Of the enrolled 1557 DCIS patients,surgical methods included modified radical mastectomy,simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation).The number of DCIS cases in our center increased (P＜0.001),so did the percentage of DCIS in annual malignant surgery cases (P=-0.026).Significant decrease was found in modified radical mastectomy (P=0.012).More than half of the patients received simple mastectomy after 2010,and more than one fifth of the patients received breast conservation surgery after 2008.About 13.99％ patients who received mastectomy had breast reconstruction.The independent influence factors of refusing breast conservation surgery were age ≥ 50(P＜0.001),medium nuclear grade (P=0.044),tumor size ＞ 15mm (P＜0.001) and spontaneous discharge (P＜0.001).Patients with smaller tumor size (≤ 15mm) and no spontaneous discharge had 4.18-fold and 7.04-fold greater preference for breast conservation surgery,respectively(OR=0.232,P＜0.001;OR=0.144,P＜0.001).There were no significant differences in RFS and LRRFS in patients with different surgical methods.Conclusion The evaluation in trends and influence factors of different surgical methods provides basis on surgical precision medicine in DCIS patients.

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Establishment of an immortalized mouse mammary epithelial cell fines

Yingchao ZHANG ; Haibing LU ; Yu WANG ; Yajing LIU ; Yue YUAN ; Xinping WANG

Chinese Journal of Endocrine Surgery.2019;13(5):364-367. doi:10.3760/cma.j.issn.1674-6090.2019.05.003

Objective To provide experimental materials for exploring the function of breast cancer susceptibility gene 2(BRCA2) gene by establishing of an mouse immortalized mammary gland epithelial cell line as a cell model system.Methods In this study,the primary mouse mammary epithelial cells were isolated and purified by enzyme digestion and differential centrifugation.The resulting primary mouse mammary gland epithelial cells were transducted with lentivirus expressing human telomerase (hTERT) gene,and screened by hygromycin B.The surviving epithelial cells were further characterized by morphology observations and cytokeratin marker detection.Results Immortalized mouse mammary epithelial cells were obtained by infection of MMECs with lentivirus expressing human telomerase(hTERT) gene,screened by hygromycin B.Morphology observations and detection of the cytokeratin marker showed the immortalized MMECs had a typical morphology of luminal epithelial cells with strong expression of cytokeratin 14.Conclusion An immortalized mouse luminal epithelial cell line is successfully established with an uniform morphology,which provides a cell model system for the future exploration on BRCA2-related tumorigenesis.

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Effect of tamoxifen on invasiveness of breast cancer SK-BR-3 cells and its mechanism

Yingbin LI ; Qian GUO ; Wenhua BAO ; Bin ZHANG

Chinese Journal of Endocrine Surgery.2019;13(5):368-371. doi:10.3760/cma.j.issn.1674-6090.2019.05.004

Objective To investigate the effect of tamoxifen (TAM) on the invasiveness of breast cancer SK-BR-3 cells and its mechanism.Methods The SK-BR-3 breast cancer cells in logarithmic growth period were cultured for 24 h by theserum-free RPMI 1640 culture medium,and then were divided into control group (serumfree RPMI 1640 medium) and TAM group(serum-freeRPMI 16400.5,2.5,12.5 mol·L-1TAM).Western blot was used to detect matrix metalloproteinase-9 (MMP-9),matrix metalloproteinase-2 (MMP-2),and vascular endothelial growth factor (VEGF) in groups.Scratch and transwelhests were used to detect the invasiveness of SK-BR-3 cells.Results The results of scratch test and Transwell experiment showed that the relative invasive ability of SKM-BR-3 cells in TAM (0.5,2.5,12.5 mol/L) group was significantly higher than that in the control group,and the difference was statistically significant (P＜0.05).The invasive ability of SK-BR-3 cells increased with the increase of TAM con centration.The results of Western blot showed that the expression levels of VEGF,MMP-9 and MMP-2 in SK-BR-3 cells of TAM group were average.It was significantly higher than the control group,and the expression levels of VEGF,MMP-9 and MMP-2 in SK-BR-3 cells increased gradually with the increase of TAM concentration.Conclusion Tamoxifen may play the role of estrogens and promote the invasiveness of SK-BR-3 breast cancer cells,via increasing the expression levels of VEGF,MMP-9 and MMP-2.

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Chemotherapeutic drugs affect methylation of ER-α in breast cancer cells by down-regulating miR-148b

Yongcheng LI ; Li SUN ; Xiaoyan MA ; Cuntao LU ; Zhengxiang HAN ; Susheng CAO

Chinese Journal of Endocrine Surgery.2019;13(5):372-377. doi:10.3760/cma.j.issn.1674-6090.2019.05.005

Objective To investigate the effects of chemotherapeutic drugs on ER-α expression and methylation in breast cancer cells.Methods Human breast cancer cells MCF-7(ER+,Luminal A) were induced by paclitaxel(PTX) and epirubicin(EPI) for more than 6 months,with an incremental dose,respectively.The expression and methylation status of ER-α in MCF-7 cells were detected before and after drug treatment.miRNAs with consistent expression changes in MCF-7 cells after two drugs' treatment were screened by microarray,and verified by quantitative PCR (qPCR).Targets of the most significantly down-regulated miRNA were analyzed by bioinformatics.miRNA inhibitor was transfected into MCF-7 cells,miRNA mimic was transfected into MCF-7/PTX and MCF-7/EPI cells,then ER-α and DNA methyltransferase 1 (DNMT1) expression were detected by Western blot,and ER-α methylation was detected by quantitative methylation-specific PCR (qMSP).Results PTX resistant MCF-7/PTX cell line and EPI resistant MCF-7/EPI cell line were established.Both drug treatments caused a decrease in ER-α protein expression and an increase in methylation levels,with up-regulation of DNMT1 and his tone deacetylase 1 (HDAC 1) expression.miRNAs with consistent expression changes in MCF-7 cells after drug treatments were screened and verified by qPCR,the most significant down-regulation among which was miR-148b.Bioinformatics analysis,and further confirmed by luciferase reporter gene assay (Luciferas) that DNMT1 was a direct target of miR-148b.miR-148b inhibitor induced decreased expression of ER-α and increased methylation level in MCF-7 cells,accompanied by increased expression of DNMT1;whereas miR-148b mimic caused an increased expression of ER-α and decreased methylation level in MCF-7/PTX and MCF-7/EPI cells,with a decreased expression of DNMT1.Conclusion Chemotherapeutic drugs (represented by PTX and EPI) induce aberrant miRNA expression in breast cancer MCF-7 cells,and down-regulate miR-148b further to attenuate the inhibition of DNMT1 expression,which promote,hypermethylation and down-regulation of ER-α.

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Experimental study and clinical significance of AR/let-7 signaling pathway in inhibiting the proliferation of triple negative breast cancer

Xiang LU ; Caiping CHEN

Chinese Journal of Endocrine Surgery.2019;13(5):378-382. doi:10.3760/cma.j.issn.1674-6090.2019.05.006

Objective To investigate the mechanism of AR/let-7 signaling pathway in inhibiting the proliferation of TNBC and its significance for survival.Methods Human breast cancer MDA-MB-453 cells were cultured in vitro and divided into experimental group and control group.The experimental group was added with androgen dihydrotestosterone(DHT),and the control group was added nothing.The cell proliferation was detected by CCK-8,cell cycle was detected by flow cytometry,AR expression was detected by Western blot,and let-7 expression was detected by real-time fluorescent quantitative PCR.The AR,let-7 expression data and survival data of TNBC patients were downloaded from the Cancer Genomes Atlas (TCGA).The expression of AR and let-7 between cancer tissues and normal breast tissues and their relationship with survival was analyzed.Results Cellular experiments showed that the proliferation rate of cancer cells in the experimental group was significantly lower than that in the control group(1.22±0.11 vs 2.26±0.23,t=7.065,P＜0.05),and the ratio of G1/S in the experimental group was greater than in the control group (1.08±0.03 vs 0.68±0.03,t=17.321,P=0.000).The AR and let-7a,b,c,and d were overexpressed in the experimental group.The TCGA data showed that AR,let-7a-1,let-7a-2,let7a-3,and let-7c were lower in breast cancer tissues than in normal tissues (P＜0.05),while let-7d was higher in breast cancer tissues (P＜0.05).The AR,let-7a-1,let-7a-2,let-7a-3,and let-7c were used to cluster the patients into high-expression group and low-expression group,and the overall survival in the high-expression group appeared to be higher,while the difference was not statistically significant (P=0.163).Conclusions The AR/let-7 signaling pathway is up-regulated by DHT activation,which blocks cells in the G1 phase and inhibits cell proliferation.Patients with high expression of AR,let-7a-1,let-7a-2,let-7a-3,and let-7c may have better overall survival.It is suggests that the AR/let-7 signaling pathway may become a new target for TNBC.

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Analysis of the performance of contrast-enhanced ultrasound for evaluating response to neoadjuvant chemotherapy in breast cancer

Yijie CHEN ; Lina TANG ; Jian LIU ; Zhongshi DU ; Yaoqin WANG ; Zhaoming ZHONG ; Zhijian HUANG ; Qiuyan HUANG ; Weiwei HUANG

Chinese Journal of Endocrine Surgery.2019;13(5):383-386. doi:10.3760/cma.j.issn.1674-6090.2019.05.007

Objective To analyze the performance of contrast-enhanced uhrasound(CEUS) in the evaluation of response to neoadjuvant chemotherapy (NAC) for breast cancer in different periods.Methods A prospective study consisting of 46 patients with invasive ductal carcinoma who received NAC and surgery subsequently was conducted.One patient underwent CEUS before NAC,after the second cycle of NAC and before surgery.CEUS outcomes were compared with histopathologic response by Kappa test using the Miller-Payne Grading(MPG) system.The changes of CEUS quantitative parameters in different periods of NAC were compared.Results 31 patients showed a good response by histopathology while 29 patients by CEUS,which showed good consistence.Kappa value was 0.713.The peak intensity (PI) of the lesions decreased significantly after the second cycle of NAC compared with that before NAC (P＜0.05).The peak intensity (PI),wash-in slope (WIS),and area under curve(AUC) of the lesions decreased significantly before surgery compared with those before NAC (P＜0.05).Conclusion CEUS shows good consistence with histopathologic outcomes.The peak intensity (PI) is a sensitive indicator of early changes after NAC.

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Clinical diagnosis and treatment of 20 cases of breast neuroendocrine carcinoma

Yonglin ZHANG ; Chao LIU ; Chaoting ZHENG ; Guanglei CHEN ; Fangming LIU ; Tiantian XU ; Zhenhai MA

Chinese Journal of Endocrine Surgery.2019;13(5):387-392. doi:10.3760/cma.j.issn.1674-6090.2019.05.008

Objective To investigate the clinical characteristics,diagnosis and treatment strategies of breast neuroendocrine carcinoma.Methods 20 cases with breast neuroendocrine carcinoma,who were admitted in Department of Breast Surgery,the Second Affiliated Hospital of Dalian Medical University from Mar.2005 to Dec.2017,were analyzed retrospectively.Results The average age of the 20 patients was(54.35±13.35) years.In aspect of surgery,18 patients received modified radical mastectomy,1 patient received total glandectomy and sentinel lymph node biopsy and stage I silicone implant breast reconstruction,and 1 patient received radical mastec tomy.In terms of pathological types,there were 5 cases (25.0％) of highly differentiated neuroendocrine carcinoma,4 cases (20.0％) of poorly differentiated neuroendocrine carcinoma (small cell carcinoma),and 11 cases (55.0％)of invasive breast cancer with neuroendocrine differentiation.In molecular typing,there were 7 cases (35.0％) of Luminal A,7 cases (35.0％) of Luminal B (HER2 negative),4 cases (20.0％) of Luminal B (HER2 positive),and one case(5.0％) of HER2 type and one case(5.0％) of Basal-like type.The positive rates of ER,PR and HER2 in this group were 90.0％,60.0％ and 25.0％ respectively.20 patients were followed up for 5 to 119 months,with an average follow-up of (59.85±24.51) months.One patient developed bone metastases in the 6th year after surgery and survived for 119 months.One patient developed pulmonary metastasis at the 20th month after surgery and died at the 28th month after surgery.So far,the remaining postoperative patients still survived and no sign of recurrence or metastasis was found.Conclusion The diagnosis of breast neuroendocrine carcinoma relies on histopathological and immunohistochemical detection.Its ER/PR positive rate is high,its molecular typing is mostly Luminal type,and neoadjuvant treatment can be performed when necessary.For specific patients whose ER or PR are positive,neoadjuvant endocrine therapy is also a well-established therapy,even the optimal results can be achieved.However,more cases are still needed for research.

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The application value of a simple stereotaxic technology in open biopsy of breast calcification with wire localization guided by X-ray

Songtao DING ; Yi ZHANG ; Xiangjun MA ; Xiangping HE ; Yan LI ; Jing QIN

Chinese Journal of Endocrine Surgery.2019;13(5):393-396. doi:10.3760/cma.j.issn.1674-6090.2019.05.009

Objective To investigate the applicafion value of a simple stereotaxic technology in open biopsy of breast calcification with wire localization guided by X-ray.Methods 36 lesions in 30 cases with calcifications on mammography underwent X-ray guided simple wire stereotaxic localization open biopsy.Results 36 lesions in 30 cases were removed completely after wire localization,among which 24 cases were removed completely by one time,accounting for 80％ (24/30)of the total,and 6 cases were removed completely by two times,accounting for 20％ (6/30)of the total.No case were removed without calcification or removed completely by more than three times.Conclusion The simple stereotaxic technology in open biopsy of breast calcification with wire localization guided by X-ray is easy to learn and safe to do,which is suitable for promotion at the grassroots hospital.

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Analysis of clinical and pathological factors in breast cancer patients with brain metastasis: a retrospective study based on SEER database

Chenyu ZHAO ; Xiaoman JIANG ; Zhenyu WANG ; Yan ZHANG

Chinese Journal of Endocrine Surgery.2019;13(5):397-403. doi:10.3760/cma.j.issn.1674-6090.2019.05.010

Objective To evaluate the impact of clinical and pathological factors on incidence and prognosis of brain metastasis from breast cancer.Methods The clinical data of 4473 stage Ⅳ breast cancer patients were collected from The Surveillance,Epidemiology,and End Results (SEER) database.All these patients were divided into brain metastasis group (n=345) and non-brain metastasis group (n=4 128).The clinical and pathological factors between the two groups were compared using x2 test and binary Logistic regression.The OS of 345 brain metastasis patients was calculated using the Kaplan-Meier method and impact of clinical and pathological factors on the survival rate was analyzed by Log-rank method.Multivariate Cox regression model was used to find out the independent risk factors.Results Between brain metastasis group and non-brain metastasis group,these following clinical and pathological factors showed the scatistical significance on brain metastasis:age,histological grade,T stage,N stage,ER,PR and HER expression (P＜0.05).Binary Logistic regression results showed that age,T stage,N stage,ER,PR were independent factors affecting brain metastasis (P＜0.05).The prognosis analysis showed that marital status,histological grade,ER,PR,molecular subtype,radiotherapy and chemotherapy,surgery at primary lesions,surgery at metastasis site,liver metastasis,lung metastasis and numbers of other organs metastasis were significantly correlated with the survival of breast cancer patients with brain metastasis (P＜0.05).Cox regression analysis showed that histological grade,ER,PR,molecular subtype,radiotherapy and chemotherapy,surgery at primary lesions,surgery at metastasis site were independent prognostic factors in breast cancer patients with liver metastasis.Conclusions Breast cancer patients with brain metastasis have a poor prognosis.Molecular subtype should be considered for prediction of prognosis for patients with brain metastasis.Radiotherapy and surgery at metastasis or primary site may improve survival of patients.

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