Anti-Cancer Agents Associated Diarrhea:Current Status and Prospects

Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.

Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients

The purpose of this study was to identify and validate circulating microRNAs （miRNAs） in human plasma for use as breast cancer （BC） biomarkers and to analyze their relationship to clinicopathologic features and its preliminary biological function. Genome-wide expression profiling of miRNAs in BC was investigated by microarray analysis, miR-155 was up-regulated greater than two-fold in BC compared with Normal Adjacent Tissue （NAT）, whereas let-7b, miR-381, miR-10b, miR-125a-Sp, miR-335, miR-205 and miR-145 were down- regulated greater than two-fold. Our hypothesis was that circulating miRNAs are also present and differentially expressed in the serum of BC patients compared to controls. Using real-time PCR （RT-PCR）, we analyzed miR-205 and miR-155 in archived serum from 30 participants, 20 with breast cancer and I0 healthy people, miR-205 was down-regulated in BC patient serum while miR-155 was up-regulated. Furthermore, we analyzed the relationship between the expression levels of these two miRNAs and the clinicopathologic parameters of BC patients. High expression of miR155 was associated with clinical stage, molecular type, Ki-67 and p53 in BC patients （P〈0.05）. By contrast, we found no significant correlation between miR-205 and BC patient clinicopathologic parameters. Functional analysis showed that ectopic expression of miR-205 significantly inhibits cell proliferation and promotes apoptosis, miR-205 was down- regulated and miR-155 was up-regulated in BC patient serum, miR-155 was positive correlated with clinical stage and 16-67 and negatively correlated with p53 status.

Adjuvant treatment for triple-negative breast cancer: a retrospective study of immunotherapy with autologous cytokine-induced killer cells in 294 patients

Objective: To examine the efficacy and safety of a sequential combination of chemotherapy and autologous cytokine-induced killer(CIK) cell treatment in triple-negative breast cancer(TNBC) patients.Methods: A total of 294 post-surgery TNBC patients participated in the research from January 1, 2009 to January 1, 2015. After adjuvant chemotherapy, autologous CIK cells were introduced in 147 cases(CIK group), while adjuvant chemotherapy alone was used to treat the remaining 147 cases(control group). The major endpoints of the investigation were the disease-free survival(DFS) and overall survival(OS). Additionally, the side effects of the treatment were evaluated.Results: In the CIK group, the DFS and OS intervals of the patients were significantly longer than those of the control group(DFS:P = 0.047;OS: P = 0.007). The multivariate analysis demonstrated that the TNM(tumor-node-metastasis) stage and adjuvant CIK treatment were independent prognostic factors for both DFS [hazard ratio(HR)= 0.520, 95% confidence interval(CI):0.271-0.998, P = 0.049;HR = 1.449, 95% CI:1.118-1.877, P = 0.005, respectively] and OS(HR=0.414, 95% CI:0.190-0.903, P = 0.027;HR= 1.581, 95% CI:1.204-2.077, P = 0.001, respectively) in patients with TNBC. Additionally, longer DFS and OS intervals were associated with increased number of CIK treatment cycles(DFS: P = 0.020;OS: P = 0.040). The majority of the patients who benefitted from CIK cell therapy were relatively early-stage TNBC patients.Conclusion: Chemotherapy in combination with adjuvant CIK could be used to lower the relapse and metastasis rate, thus effectively extending the survival time of TNBC patients, especially those at early stages.

Accessory Breast Cancer Occurring Concurrently with Bilateral Primary Invasive Breast Carcinomas:A Report of Two Cases and Literature Review

The development of accessory breast tissue,which is found anywhere along the milk line,is attributed to the failure of milk line remnants to regress during embryogenesis.Primary tumors may arise from any ectopic breast tissue.Accessory breast cancer occurring concurrently with primary invasive breast cancer is extremely rare.Two such cases were reported in this article.One was a 43-year-old Chinese female who exhibited bilateral breast cancer(invasive ductal carcinoma,not otherwise specified,IDC-NOS) and an accessory breast carcinoma(IDC-NOS) incidentally identified in her left axilla.The ectopic breast tissue in her right axilla presented with adenosis.The patient was surgically treated,followed by postoperative docetaxel epirubicin(TE) chemotherapy.The second case was a 53-year-old Chinese female with bilateral breast cancer(apocrine carcinoma) accompanied by an accessory breast carcinoma(IDC-NOS) in her right axilla that was also incidentally identified.The patient was surgically treated after three doses of cyclophosphamide epirubicin docetaxel(CET) neoadjuvant chemotherapy,followed by adjuvant chemotherapy of the same regimen.

Identification of the Interaction between P-Glycoprotein and Anxa2 in Multidrug-resistant Human Breast Cancer Cells

Objective To explore the interaction of Anxa2 with P-Glycoprotein （P-gp） in the migration and invasion of the multidrug-resistant （MDR） human breast cancer cell line MCF-7/ADR. Methods A pair of short hairpin RNA （shRNA） targeting P-gp was transfected into MCF-7/ADR cells, and monoclonal cell strains were screened. The expression of P-gp was detected by Western blot. Transwell chambers were used to observe the cell migration capacity and invasion ability. The interaction between P-gp and Anxa2 was examined by immunoprecipitation and immunofluorescence confocal microscopy analyses. Results P-gp expression was significantly knocked down, and there were notable decreasing trends in the migration and invasion capability of MDR breast cancer cells （P〈0.05）. There was a close interaction between Anxa2 and P-gp. Conclusions MCF-7/ADR is an MDR human breast cancer cell line with high migration and invasion abilities. The knockdown of P-gp notably impaired the migration and invasion abilities of the tumor cells. The interaction of Anxa2 with P-pg may play an important role in time enhanced invasiveness of MDR human breast cancer cells.

An exploration for quantification of overdiagnosis and its effect for breast cancer screening

Objective: To redefine overdiagnosis and reestimate the proportion of overdiagnosis of breast cancer caused by screening based on the Surveillance, Epidemiology, and End Results(SEER, 1973-2015) Program data.Methods: The breast cancer diagnosed before 1977 was defined as the no-screening cohort since America had initiated breast cancer screening from 1977. The breast cancer diagnosed in 1999 was defined as the screening cohort due to no increases in both the proportion of early-stage breast cancer until 1999 and the overall survival of early-stage breast cancer diagnosed over the three years since 1999. The magnitude of overdiagnosis was calculated as the difference in the proportions of early-stage breast cancer patients with long-time(15-year) survival to all breast cancer patients between two cohorts.Results: Over 23 years before and after widespread screening in America, the proportion of early-stage breast cancer patients increased from 52.1%(16,891/32,443) to 72.7%(16,021/22,025)(P<0.001). The 15-year survival rate of early-stage breast cancer patients increased from 51.1% to 61.5%(P<0.001), while the proportions of earlystage breast cancer patients with long-time survival to all breast cancer patients increased from 26.6%(52.1%×51.1%) to 44.7%(72.7%×61.5%). Assuming no improvements in cancer screening technology and treatment technology, 18.1%(44.7%-26.6%) of breast cancer patients were overdiagnosed associated with screening. The age-specific overdiagnosis rates were 18.9%, 24.7%, 24.5%, 20.5%, and 8.3% for breast cancer patients aged 40-49, 50-59, 60-69, 70-74, and ≥75 years old, respectively.Conclusions: Overdiagnosis caused by mammographic screening is probably overestimated in current screening practices. Further trials with more sophisticated designs and analyses are needed to validate our findings in the future.

Multicenter phaseⅡstudy of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis

Objective:Breast cancer(BC)with chest wall metastasis(CWM)usually shows rich neovascularization.This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2(HER2)-negative advanced BC involving CWM.Methods:This trial involved four centers in China and was conducted from September 2016 to March 2020.Patients received apatinib 500 mg/d[either alone or with endocrine therapy if hormone receptor-positive(HR+)]until disease progression or unacceptable toxicity.Progression-free survival(PFS)was the primary endpoint.Results:We evaluated 26 patients for efficacy.The median PFS(mPFS)and median overall survival(mOS)were4.9[range:2.0-28.5;95%confidence interval(95%CI):2.1-8.3]months and 18(range:3-55;95%CI:12.9-23.1)months,respectively.The objective response rate(ORR)was 42.3%(11/26),and the disease-control rate was76.9%(20/26).In the subgroup analysis,HR+patients compared with HR-negative patients had significantly improved mPFS of 7.0(95%CI:2.2-11.8)months vs.2.3(95%CI:1.2-3.4)months,respectively(P=0.001);and mPFS in patients without or with chest wall radiotherapy was 6.4(95%CI:1.6-19.5)months vs.3.0(95%CI:1.3-4.6)months,respectively(P=0.041).In the multivariate analysis,HR+status was the only independent predictive factor for favorable PFS(P=0.014).Conclusions:Apatinib was highly effective for BC patients with CWM,especially when combined with endocrine therapy.PFS improved significantly in patients with HR+status who did not receive chest wall radiotherapy.However,adverse events were serious and should be carefully monitored from the beginning of apatinib treatment.

Development and evaluation of the screening performance of a low-cost high-risk screening strategy for breast cancer

Objective:To develop and evaluate the screening performance of a low-cost high-risk screening strategy for breast cancer in low resource areas.Methods:Based on the Multi-modality Independent Screening Trial,6 questionnaire-based risk factors of breast cancer(age at menarche,age at menopause,age at first live birth,oral contraceptive,obesity,family history of breast cancer)were used to determine the women with high risk of breast cancer.The screening performance of clinical breast examination(CBE),breast ultrasonography(BUS),and mammography(MAM)were calculated and compared to determine the optimal screening method for these high risk women.Results:A total of 94 breast cancers were detected among 31,720 asymptomatic Chinese women aged 45–65 years.Due to significantly higher detection rates(DRs)and suitable coverage of the population,high risk women were defined as those with any of 6 risk factors.Among high risk women,the DR for BUS[3.09/1,000(33/10,694)]was similar to that for MAM[3.18/1,000(34/10,696)],while it was significantly higher than that for the CBE[1.73/1,000(19/10,959),P=0.002].Compared with MAM,BUS showed significantly higher specificity[98.64%(10,501/10,646)vs.98.06%(10,443/10,650),P=0.001],but no significant differences in sensitivity[68.75%(33/48)vs.73.91%(34/46)],positive prediction values[18.54%(33/178)vs.14.11%(34/241)],and negative prediction values[99.86%(10,501/10,516)vs.99.89%(10,443/10,455)].Further analyses showed no significant difference in the percentages of early stage breast cancer[53.57%(15/28)vs.50.00%(15/30)],lymph node involvement[22.73%(5/22)vs.28.00%(7/25)],and tumor size≥2 cm[37.04%(10/27)vs.29.03%(9/31)]between BUS and MAM.Subgroup analyses stratified by breast densities or age at enrollment showed similar results.Conclusions:The low-cost high-risk screening strategy based on 6 questionnaire-based risk factors was an easy-to-use method to identify women with high risk of breast cancer.Moreover,BUS and MAM had comparable screening performances among high risk women.

Effects of postmastectomy radiotherapy on prognosis in different tumor stages of breast cancer patients with positive axillary lymph nodes

Objective: To explore the effects of postmastectomy radiotherapy(PMRT) on the locoregional failure-free survival(LRFFS) and overall survival(OS) of breast cancer patients under different tumor stages and with one to three positive axillary lymph nodes(ALNs). Methods: We conducted a retrospective review of 527 patients with one to three positive lymph nodes who underwent modified radical or partial mastectomy and axillary dissection from January 2000 to December 2002. The patients were divided into the T1-T2 N1 and T3-T4 N1 groups. The effects of PMRT on the LRFFS and OS of these two patient groups were analyzed using SPSS 19.0, Pearson's χ2-test, Kaplan-Meier method, and Cox proportional hazard model. Results: For T1-T2 N1 patients, no statistical significance was observed in the effects of PMRT on LRFFS [hazard ratio(HR)=0.726; 95% confidence interval(CI): 0.233-2.265; P=0.582] and OS(HR=0.914; 95% CI: 0.478-1.745; P=0.784) of the general patients. Extracapsular extension(ECE) and high histological grade were the risk factors for LRFFS and OS with statistical significance in multivariate analysis. Stratification analysis showed that PMRT statistically improved the clinical outcomes in high-risk patients [ECE(+), LRFFS: P=0.026, OS: P=0.007; histological grade III, LRFFS: P<0.001, OS: P=0.007] but not in low-risk patients [ECE(–), LRFFS: P=0.987, OS: P=0.502; histological grade I-II, LRFFS: P=0.816, OS: P=0.296]. For T3-T4 N1 patients, PMRT effectively improved the local control(HR=0.089; 95% CI: 0.210-0.378; P=0.001) of the general patients, whereas no statistical effect was observed on OS(HR=1.251; 95% CI: 0.597-2.622; P=0.552). Absence of estrogen receptors and progesterone receptors(ER/PR)(–) was an independent risk factor. Further stratification analysis indicated a statistical difference in LRFFS and OS between the high-risk patients with ER/PR(–) receiving PMRT and not receiving PMRT [ER/PR(–), LRFFS: P=0.046, OS: P=0.039]. However, PMRT had a beneficial effect on the reduction of locoregional recurrence(LRR) but not in total mortality [ER/PR(+), LRFFS: P<0.001, OS: P= 0.695] in T3-T4 N1 patients with ER/PR(+) who received endocrine therapy. Conclusion: PMRT could reduce ECE(+), histological grade III-related LRR, and total mortality of T1-T2 N1 patients. T3-T4 N1 patients with ER/PR(–) could benefit from PMRT by improving LRFFS and OS. However, PMRT could only reduce LRR but failed to improve OS for T3-T4 N1 patients with ER/PR(+) who received endocrine therapy.

The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families

Objective:Approximately 5%–10%of breast cancer(BC)patients display familial traits that are genetically inherited among the members of a family.The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families.Methods:Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families.Results:Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8%(96/116)of the cases.Among these,80.8%of the mutated genes were related to DNA damage repair.Fourteen possible disease-causing variants were identified in 13 of 27 BC families.Only 25.9%(7/27)of the BC families exhibited hereditary deficiency in BRCA1/2 genes,while 22.2%of the BC families exhibited defects in non-BRCA genes.In all,41.7%(40/96)of the mutation carriers had BRCA mutations,88.5%(85/96)had non-BRCA mutations,and 30.2%(29/96)had both BRCA and non-BRCA mutations.The BC patients with BRCA mutations had a higher risk of axillary lymph node metastases than those without mutations(P<0.05).However,the BC patients with non-BRCA mutations frequently had a higher occurrence of benign breast diseases than those without mutations(P<0.05).Conclusions:In addition to BRCA1/2,genetic variants in non-BRCA DNA repair genes might play significant roles in the development of familial/hereditary BC.Therefore,profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.

Tyrosine 23 Phosphorylation of Annexin A2 Promotes Proliferation,Invasion,and Stat3 Phosphorylation in the Nucleus of Human Breast Cancer SK-BR-3 Cells

Objective To investigate the role of tyrosine 23 （Tyr23） phosphorylation of Annexin A2 （Anxa2） in regulating the proliferation and invasion of human breast cancer SK-BR-3 cells. Methods A panel of lentivirus plasmids expressing Anxa2-wide type （Ana2-WT）, Anxa2-Y23A, and Anxa2-Y23D was generated and infected with SK-BR-3 cells. The monoclonal strains were screened. The expression of Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D was determined by Western blot analysis. The ability of the cells to proliferate was detected through an MTT [3-（4,5-Dimethylthiazol- 2-yl）-2,5-diphenyltetrazolium bromide] test. Boyden chamber assays were employed to examine migration and invasion abilities. The interaction between Anxa2 and Stat3 was analyzed by immunoprecipitation analyses. Nucleoprotein and cytosolic protein were extracted from SK-BR-3, Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D cells to analyze the expression and localization of Stat3 phosphorylation. Results The monoclonal strains constitutively expressing Anxa2-WT, Anxa2-Y23A, and Anxa2-Y23D were screened. Both Anxa2-WT and Anxa2-Y23D enhanced the proliferation, migration and invasion abilities of SK-BR-3 cells （P〈0.05）. Immunoprecipitation analysis revealed that Anxa2 and Stat3 interacted with each other, and the expression of Stat3 phosphorylation in the nucleus was enhanced by Anxa2-Y23D. Conclusions Tyr23 phosphorylation of Anxa2 promotes the proliferation and invasion of human breast cancer SK-BR-3 cells and the phosphorylation of Stat3 in the nucleus.

Prognostic and Predictive Factors of Early Breast Cancer

OBJECTIVE To identify risk factors for relapse and death in patients with T1 to T2 breast cancer with 0-3 positive axillary lymph nodes.METHODS The case files of 540 breast cancer patients with T1-T2 tumors with 0-3 positive nodes were reviewed retrospectively. Ten-year locoregional recurrence （LRR）, distant recurrence （DR）, disease-free survival （DFS） and overall survival （OS） of the patients were analyzed. Univariate statistical analysis and Cox proportional hazards models were carried out with SPSS so ware v.16.0.RESULTS The median follow-up of all the patients was 7.2 years. On multivariate analysis, 〉 20% positive axillary nodes was the only variable that influenced LRR adversely （hazard ratio[HR], 12.816; 95% confidence interval, 4.657-35.266, P 〈 0.001）; 〉 20% positive axillary nodes and ductal carcinoma were variables that influenced DR adversely （HR, 11.088, 95% confidence interval, 3.807-32.297, P 〈 0.001; HR, 0.390, 95% confidence interval, 0.179-0.851, P = 0.018）; 1-3 positive axillary nodes and 〉 20% positive axillary nodes were the only variables that had negative e. ect on 10-year OS （HR, 2.110, 95% confi dence interval, 1.364-3.264, P = 0.001; HR, 10.244, 95% confidence interval, 3.497-30.011, P 〈 0.001） and they were also adverse prognostic variables on 10-year DFS （HR, 1.634, 95% confidence interval, 1.171-2.279, P = 0.004; HR, 7.339, 95% confi dence interval,2.906-18.530, P 〈 0.001）.CONCLUSION Axillary lymph nodal status is the only risk factor with a signifi cant impact on 10-year LRR, DR, OS and DFS.Patients with T1-T2 breast cancer with 0-3 positive lymph nodes have the LRR and DR of over 10 years, and the OS and DFS of less than 10 years, compared to patients with negative lymph nodes.Histology in primary tumors is a signifi cant prognostic factor for the 10-year DR.

Clonal Analysis of Peripheral Papilloma and Cancerous Cells of the Breast

OBJECTIVE Because almost all malignancies represent monoclonal proliferations, we have studied the clonal status of peripheral papillomas （peri-PM）, ductal carcinomas in situ （DCIS）, and normal breast tissues to explore a reliable way to distinguish benign and malignant （or pre-malignant） cases previously diagnosed morphologically. METHODS Twenty-six cases of peri-PM, 25 cases of peri-PM with atypical ductal hyperplasia （ADH）, 27 cases of DCIS, 16 cases of developed canceration and 20 specimens of normal tissue were examined in the study. The clonal status of these tissues was studied using an assay based on inactivation mosaicism of the lenth-polymorphic X-chromosomes at the androgen receptor （AR） locus. RESULTS Loss of polymorphism at the AR locus was found in all DCIS cases and 10 cases （10/25, 40.0%） of peri-PM with ADH, in.dicating the monoclonality of the tumors. Twenty-four out of 26 （92.3%） cases with peri- PM and 19 specimens of normal tissue were shown to be polyclonal. In 16 cases of developed Canceration, identical X chromosome inactivation （monoclonal alterations） was observed from both the peri-PM with ADH part, and the DCIS part in each Case. CONCLUSION These results contribute to the understanding of the genetic changes of peri-PM, and confirm the peri-PM with ADH as a precancerous lesion of the breast. Clonal analysis might be a useful modality to screen high-risk cases from precancerous lesions or to distinguish between benign hyperplasia and early carcinoma.

In Vivo Selection of Phage Sequences and Characterization of Peptide-specific Binding to Breast Cancer Cells

OBJECTIVE To screen specific polypeptide target binding to breast cancer xenografts in vivo from a phage-displayed peptide library in order to provide peptide sequences for breast cancer tumor-targeting diagnosis and therapy. METHODS A mouse model for carrying breast cancer xenografts was established using Tientsin Albinao Ⅱ mice （TA Ⅱ）. A 12-peptide library was biopanned through 4 rounds. Phages were recovered and titrated from tumor xenografts and control tissue （liver）. The distribution of phages was detected by immunohistochemical staining. RESULTS Phage homing to breast cancer was enriched through 4 rounds of biopanning, being 14-fold of that recovered from liver tissue. A peptide sequence, ASANPFPTKALL was characterized by randomly picked-up clones which appeared most frequently. Immunohistochemical staining revealed phage localization in cancer xenografts 40 min after injection of the enriched phages. When a specific phage was tested individually, the phage reclaimed from breast cancer xenografts was 14 times as those from control tissues. CONCLUSION Tumor-specific homing peptides may provide an effective tool for breast cancer target therapy. The in vivo phage display selection technique employed in this study was feasible and applicable to screening peptides that home to breast cells.

The Hippo/YAP signaling pathway:the driver of cancer metastasis

Despite major improvements in cancer survival,metastasis is responsible for almost 90%of cancer-related mortality^(1,2).Nonetheless,the pathogenesis and molecular mechanisms of cancer metastasis remain poorly understood.

SHP2 promotes proliferation of breast cancer cells through regulating Cyclin D1 stabilityviathe PI3K/AKT/GSK3β signaling pathway

Objective:The tyrosine phosphatase SHP2 has a dual role in cancer initiation and progression in a tissue type-dependent manner.Several studies have linked SHP2 to the aggressive behavior of breast cancer cells and poorer outcomes in people with cancer.Nevertheless,the mechanistic details of how SHP2 promotes breast cancer progression remain largely undefined.Methods:The relationship between SHP2 expression and the prognosis of patients with breast cancer was investigated by using the TCGA and GEO databases.The expression of SHP2 in breast cancer tissues was analyzed by immunohistochemistry.CRISPR/Cas9 technology was used to generate SHP2-knockout breast cancer cells.Cell-counting kit-8,colony formation,cell cycle,and EdU incorporation assays,as well as a tumor xenograft model were used to examine the function of SHP2 in breast cancer proliferation.Quantitative RT-PCR,western blotting,immunofluorescence staining,and ubiquitination assays were used to explore the molecular mechanism through which SHP2 regulates breast cancer proliferation.Results:High SHP2 expression is correlated with poor prognosis in patients with breast cancer.SHP2 is required for the proliferation of breast cancer cellsin vitro and tumor growthin vivo through regulation of Cyclin D1 abundance,thereby accelerating cell cycle progression.Notably,SHP2 modulates the ubiquitin–proteasome-dependent degradation of Cyclin D1viathe PI3K/AKT/GSK3βsignaling pathway.SHP2 knockout attenuates the activation of PI3K/AKT signaling and causes the dephosphorylation and resultant activation of GSK3β.GSK3βthen mediates phosphorylation of Cyclin D1 at threonine 286,thereby promoting the translocation of Cyclin D1 from the nucleus to the cytoplasm and facilitating Cyclin D1 degradation through the ubiquitin–proteasome system.Conclusions:Our study uncovered the mechanism through which SHP2 regulates breast cancer proliferation.SHP2 may therefore potentially serve as a therapeutic target for breast cancer.

Clinicopathologic and molecular characteristics of 44 patients with pure secretory breast carcinoma

Objective: Secretory breast carcinoma(SBC) is a rare type of breast malignancy, accounting for less than 0.02% of all infiltrating breast malignancies. The pure SBC, a type of SBC without another type of breast malignant neoplasm, is particularly rare. This study aimed to investigate the clinicopathologic and molecular features of pure SBC.Methods: The main pathological parameters such as estrogen receptor(ER), progesterone receptor(PR), and human epithelial growth factor receptor 2(C-erbB-2) were detected by immunohistochemistry(IHC), and the clinicopathologic and prognostic difference were compared with invasive ductal carcinoma(IDC). Fluorescent in situ hybridization(FISH) and reverse transcription polymerase chain reaction(RT-PCR) was performed to identify the ETV6-NTRK3 rearrangement of SBC.Results: We found that the positivity rates of ER, PR, C-erbB-2, p53, and S-100 were 47.7%(21/44), 52.3%(23/44), 36.4%(16/44), 27.3%(12/44), and 95.5%(42/44), respectively, which were higher than those reported in previous studies. Special periodic acid-Schiff analysis was performed in 36 patients, and the value of the Ki-67 index ranged from 1% to 50%(mean value:10%). Interestingly, most patients with pure SBC harbored an ETV6-NTRK3 rearrangement with an 88.6%(39/44) expression rate. Compared with IDC, the tumor size of most patients with SBC was larger than 2 cm(P = 0.024). Ultrasound showed benign lesions, and the total misdiagnosis rate was higher(P = 0.020). Although the pathological classification was mostly triple-negative breast cancers(P = 0.036), there was less metastasis(P = 0.029), and the overall prognosis was better than that of the IDC group.Conclusions: Although axillary lymph node metastasis, local recurrence, or distant metastasis may occur, SBC is also considered an indolent neoplasm with a good prognosis. Once diagnosed, surgical treatment should be performed as soon as possible,followed by appropriate adjuvant chemotherapy, irradiation, and endocrine therapies.

Active and passive smoking with breast cancer risk for Chinese females: a systematic review and meta-analysis

Previous studies suggested that smoking and passive smoking could increase the risk of breast cancer, but the results were inconsistent, especially for Chinese females. Thus, we systematically searched cohort and case-control studies investigating the associations of active and passive smoking with breast cancer risk among Chinese females in four English databases(PubMed, Embase, ScienceDirect, and Wiley) and three Chinese databases(CNKI, WanFang, and VIP). Fifty-one articles(3 cohort studies and 48 casecontrol studies) covering 17 provinces of China were finally included in this systematic review. Among Chinese females, there was significant association between passive smoking and this risk of breast cancer [odds ratio(OR): 1.62; 95% confidence interval(CI): 1.39–1.85; I2 = 75.8%, P < 0.001; n = 26] but no significant association between active smoking and the risk of breast cancer(OR: 1.04; 95% CI: 0.89–1.20; I2 = 13.9%, P = 0.248; n = 31). The OR of exposure to husband's smoking and to smoke in the workplace was 1.27(95% CI: 1.07–1.50) and 1.66(95% CI: 1.07–2.59), respectively. The OR of light and heavy passive smoking was 1.11 and 1.41, respectively, for women exposed to their husband's smoke(< 20 and ≥ 20 cigarettes per day), and 1.07 and 1.87, respectively, for those exposed to smoke in the workplace(< 300 and ≥ 300 min of exposure per day). These results imply that passive smoking is associated with an increased risk of breast cancer, and the risk seems to increase as the level of passive exposure to smoke increases among Chinese females. Women with passive exposure to smoke in the workplace have a higher risk of breast cancer than those exposed to their husband's smoking.

MicroRNA and histopathological characterization of pure mucinous breast carcinoma

Objective: Pure mucinous breast carcinoma (PMBC) is an uncommon histological type of breast cancer characterized by a large amount of mucin production. MicroRNA (miRNA) is a large class of small noncoding RNA of about 22 nt involved in the regulation of various biological processes. This study aims to identify the miRNA expression profile in PMBC. Methods: MiRNA expression profiles in 11 PMBCs were analyzed by miRNA-microarray and real-time polymerase chain reaction (PCR). Thirty-one PMBCs and 27 invasive ductal carcinoma of no special types (IDC-NSTs) were assessed by immunohistochemistry using antibodies against ER, PR-progesterone receptor, HER2, Ki-67, Bcl-2, p53, PCNA, and CK5 and 6. Results: We analyzed the miRNA expression in 11 PMBCs and corresponding normal tissues using miRNA-microarray and real-time PCR, and found that miR-143 and miR-224-5p were significantly downregulated in mucinous carcinoma tissue. Compared with IDC-NSTs, PMBC showed a significantly higher ER positive rate, lower HER-2 positive rate, and lower cell proliferation rates. Conclusions: To our knowledge, this is the first study to demonstrate the miRNA expression profile of PMBC, and our findings may lead to further understanding of this type of breast cancer.

Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia （FEA）, atypical ductal hyperplasia （ADH）, and lownuclear grade ductal carcinoma in situ （DCIS）. The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to low- nuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations--most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.