Objective: By observing the treatment and nursing care of a patient with Grade IV capsular contracture following breast cancer expander implantation and subsequent Stage II reconstruction, we aim to analyze the reason...Objective: By observing the treatment and nursing care of a patient with Grade IV capsular contracture following breast cancer expander implantation and subsequent Stage II reconstruction, we aim to analyze the reasons for the formation of capsular contracture after Stage I expander implantation and prevent its recurrence following Stage II reconstruction. Methods: In May 2020, the patient noticed an increase in the size of a breast mass. In August, she underwent AC-THP neoadjuvant chemotherapy, followed by a “right breast-conserving nipple-areolar subglandular excision + right axillary lymph node dissection + expander implantation” surgery in November 2020. Radiation therapy began in January 2021. During radiation therapy, the patient experienced severe breast hardening, distortion, tenderness, and was diagnosed with Grade IV capsular contracture. To relieve the capsular contracture, the patient underwent a “contracted capsule incision and release procedure + removal of the right breast expander + right breast implantation” surgery in July 2021. Postoperatively, measures were taken to prevent incision infection, emphasizing aseptic techniques, ensuring smooth negative pressure drainage, reducing skin flap tension, monitoring skin flap blood supply, actively preventing subcutaneous effusion and hematoma, and applying appropriate compression dressings. Results: The patient was discharged after the removal of the drainage tube. During the postoperative follow-up at 3 and 6 months, there was no recurrence of capsular contracture, and the breast appeared full, upright, and relatively soft. There were no complications such as hematoma, infection, breast implant rupture, breast sagging, or displacement. The patient had a good outcome without additional financial or surgical burdens. Conclusion: The occurrence of Grade IV capsular contracture in the patient is generally related to infection after Stage I expander implantation, improper compression dressing, excessive saline injection causing content infiltration, and radiation therapy. Therefore, it is recommended to enhance the intraoperative and postoperative prophylactic use of antibiotics after Stage I expander implantation. Intermittent saline injection after surgery, with the amount of saline gradually increasing rather than filling all at once, is advisable. This helps the breast tissue gradually adapt to expansion, reducing the risk of capsular contracture. Postoperatively, patients should be instructed to wear pressure garments and breast elastic bandages while intensifying breast monitoring during radiation therapy and increasing postoperative follow-up.展开更多
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 pr...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-5p, 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 10 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 ki-67 and negatively correlated with p53 status.展开更多
Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deace...Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.展开更多
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 ...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.展开更多
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 breas...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.展开更多
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 t...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.展开更多
Breast cancer is one of the most common malignancies in women.The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality.In this study,we tried to explore the role of circul...Breast cancer is one of the most common malignancies in women.The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality.In this study,we tried to explore the role of circulating tumor cell(CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer;meanwhile,we attempted to assess the concept of "biological complete remission"(bCR) in this regard.A 56-year-old patient with breast cancer(T2N1M1,stage IV left breast cancer,with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab.Then,she underwent CTC detection and PET/CT for efficacy evaluation.CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer.The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological(pathological) complete remission.The integrated application of the concepts including bCR,imageological CR,and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.展开更多
AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patien...AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.展开更多
A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and wa...A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.展开更多
Objective: The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone receptor-positive early breast cancer.Methods: A retrospective analysis of 327 patients aged...Objective: The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone receptor-positive early breast cancer.Methods: A retrospective analysis of 327 patients aged ≥65 years, with stage I-II, hormone receptor-positive breast cancer who underwent breast-conserving surgery and received endocrine therapy(ET) or radiotherapy plus endocrine therapy(ET+RT) was performed. Both groups were divided into luminal A type and luminal B type subgroups. Evaluation criteria were 5-year disease-free survival(DFS), local relapse rate(LRR), overall survival(OS), and distant metastasis rate(DMR).Results: There were significant differences in 5-year DFS [hazard ratio(HR)=1.59, 95% confidence interval(95% CI), 1.15-2.19;P=0.005] and LRR(HR=3.33, 95% CI, 1.51-7.34;P=0.003), whereas there were no significant differences in OS and DMR between ET group and ET+RT group. In luminal A type, there was no significant difference in 5-year DFS, LRR, OS and DMR between ET group and ET+RT group. In luminal B type,there were statistically significant differences in 5-year DFS(HR=2.19, 95% CI, 1.37-3.49;P=0.001), LRR(HR=5.45, 95% CI, 1.65-17.98;P=0.005), and OS(HR=1.75, 95% CI, 1.01-3.05;P=0.048) between ET group and ET+RT group. In the ET group, there were significant differences between luminal A type and luminal B type in5-year DFS(HR=1.84, 95% CI, 1.23-2.75;P=0.003) and OS(HR=1.76, 95% CI, 1.07-2.91;P=0.026).Conclusions: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly patients, whereas luminal A type elderly patients do not benefit from radiotherapy.Without radiotherapy, luminal A type patients have better DFS and OS than luminal B type patients.展开更多
Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4% to 1.3% has been reported in literature. The primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and ...Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4% to 1.3% has been reported in literature. The primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and malignant melanoma. In this report, two cases of pulmonary metastasis to the breast were presented. A 40-year-old female manifested a right breast mass of 2-month duration. After physical examination was performed, a poorly defined mass was noted in the upper outer quadrant of the right breast. Another 49-year-old female manifested right breast mass of 5-day duration. A poorly defined mass was noted in the lower inner quadrant of the right breast. Mammography results also revealed breast cancer. The patients underwent local excision. After histological and immunohistochemical analyses were conducted, a primary lung carcinoma that metastasized to the breast was diagnosed. An accurate differentiation of metastasis to the breast from primary breast cancer is very important because the treatment and prognosis of the two differ significantly.展开更多
Objective:Although circulating tumor cells(CTCs)have been well-established as promising prognostic biomarkers in both early breast cancer and metastatic settings,little is known regarding the prognostic relevance of C...Objective:Although circulating tumor cells(CTCs)have been well-established as promising prognostic biomarkers in both early breast cancer and metastatic settings,little is known regarding the prognostic relevance of CTCs in the long-term postoperative monitoring of patients with non-metastatic breast cancer(non-MBC).In this study,we investigated the associations of CTCs with clinicopathological features and metabolic-related variables,such as obesity and hyperglycemia.Methods:In this retrospective study,we recruited 264 patients with postoperative stage Ⅰ–Ⅲ breast cancer at Guangdong General Hospital from January 2009 to December 2015.The prevalence and number of CTCs were assessed using the Cell Search System at a median time of 19.0 months[interquartile range(IQR),7.8–33.0]after surgery.The CTC assay results were correlated with the clinicopathological features and metabolic-related variables.A multivariate logistic regression analysis was performed to further determine the independent predictors of CTCs.Results:CTCs were detected in 10.6%of all patients.The positive rate of CTCs in patients with infiltrating ductal carcinoma was lower than that in patients with other pathological types(9.0%vs.28.6%,P=0.020).More importantly,the presence of CTCs was correlated with blood glucose level(P=0.015)and high-density lipoprotein level(P=0.030).The multivariate logistic regression analysis showed that the pathological type[odds ratio(OR):1.757,95%CI:1.021–3.023;P=0.042]and blood glucose level(OR:1.218,95%CI:1.014–1.465;P=0.035)were independent predictors of the presence of CTCs.Conclusions:This study revealed potential associations between CTCs and metabolic-related factors in Chinese patients with non-MBC and supports the hypothesis that metabolic dysfunction in breast cancer patients might influence the biological activity of metastatic breast cancer,leading to a higher prevalence of CTCs.展开更多
Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the dru...Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.Methods:The expression of drug resistance genes including Topo Ⅱ,GST-π,P-gp,LRP,and CD133 were detected with immunohistochemistry in a tissue microarray.Drug sensitivity tests included those for paclitaxel,epirubicin,carboplatin,vinorelbine,and fluorouracil and were conducted on primary cancer tissue cells and cell lines,including the T47 D,BT-474,and MDA-MB-231 cells and human breast cancer xenografts in nude mice.Results:The different drug resistant genes Topo Ⅱ,GST-π,P-gp,and LRP were differentially expressed among different molecular subtypes of breast cancers(P<0.05).Positive expression of CD133 was highest in basal-like breast cancer(P<0.05).Kaplan-Meier survival analysis showed that positive expressions of Topo Ⅱ and CD133 both correlated with shorter disease-free survival(DFS)(P<0.05)and overall survival(P<0.05),and positive expression of LRP correlated only with shorter DFS(P<0.05).BT-474 showed chemosensitivity to paclitaxel and epirubicin,while MDA-MB-231 showed chemosensitivities to paclitaxel,epirubicin,carboplatin,and fluorouracil(T/C≤50%).The basal-like and HER2+breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells(P<0.05).Conclusions:The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.展开更多
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 ge...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.展开更多
In this work, patterned macropores with a diameter larger than 100 μm were introduced to pristine three-dimensional (3D) nanofibrous bacterial cellulose (BC) scaffolds by using the infrared laser micromachining techn...In this work, patterned macropores with a diameter larger than 100 μm were introduced to pristine three-dimensional (3D) nanofibrous bacterial cellulose (BC) scaffolds by using the infrared laser micromachining technique in an attempt to create an in vitro model for the culture of breast cancer cells. The morphology, pore structure, and mechanical performance of the obtained patterned macroporous BC (PM-BC) scaffolds were characterized by scanning electron microscopy (SEM), mercury intrusion porosimeter, and mechanical testing. A human breast cancer cell (MDA-MB-231) line was cultured onto the PM-BC scaffolds to investigate the role of macropores in the control of cancer cell behavior. MTT assay, SEM, and hematoxylin and eosin (H&E) staining were employed to determine cell adhesion, growth, proliferation, and infiltration. The PM-BC scaffolds were found to be able to promote cellular adhesion and proliferation on the scaffolds, and further to allow for cell infiltration into the PM-BC scaffolds. The results demonstrated that BC scaffolds with laser-patterned macropores were promising for the in vitro 3D culture of breast cancer cells.展开更多
Reports of BRCA2 genetic mutations on the prognosis of familial breast cancer(BC) patients have been contradictory. True difference in survival,if it exists,would have important implications for genetic counseling and...Reports of BRCA2 genetic mutations on the prognosis of familial breast cancer(BC) patients have been contradictory. True difference in survival,if it exists,would have important implications for genetic counseling and in treatment of hereditary BC. The purpose of this study was to compare overall survival rate(OSR) among BRCA2 mutation carriers,non-carriers and sporadic BC patients. We searched the PUBMED and EMBASE databases and retrieved 4529 articles using keywords that included breast cancer,BRCA,prognosis and survival. Nine articles were selected for systematic review and among them 6 were included in our meta-analysis. We used the fixed and random effect models to calculate the summary odds ratio(OR) and corresponding 95% confidence interval(CI). BRCA2 mutation carriers had significantly higher long-term OSR than non-carriers(OR=0.69 [95% CI=0.5–0.95]),while both short-term and long-term OSR of BRCA2 mutation carriers did not differ from those of patients with sporadic disease(OR=1.11 [95% CI=0.74–1.65]; 0.85 [95% CI=0.38–1.94],respectively). For BC-specific survival rate(BCSSR),BRCA2 mutation carriers had a similar BCSSR to the non-carriers(OR=0.61 [95% CI=0.28–1.34]). There was no significant difference in disease-free survival(DFS) between BRCA2 mutation carriers and patients with sporadic disease. Our results suggest that BRCA2 mutation increases long-term OSR in hereditary BC,which reminds us a new prospect of management of the disease.展开更多
Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the a...Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer patients.Methods: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation.Conclusions: The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing(NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.展开更多
OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 trea...OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 treated in the Cancer Hospital of Tianjin Medical University were analyzed.The Her-2,ER and PR status was determined using immunohistochemistry.Of the total cases,one group was identifi ed as triple negative breast cancer,ie defi ned as ER,PR and Her-2 negative.The other group was non-triple-negative breast cancer.Clinicopathologic features of the groups were compared and 5-year disease-free survival(DFS) analyzed by the Kaplan-Meier method.RESULTS Of the total cases,21.4%(109/509) of cases were found to be triple-negative while 78.6%(400/509) were non-triple-negative.The triple negative group had higher incidence rates than the non-triple-negative group of the medullary type and Grade Ⅲ tumors(P < 0.05).There was no other difference in the clinicopathologic features between the 2 groups.From follow-up to June,2007,21.1%(23/109) of the triple-negative group and 12.7%(51/400) of the non-triple negative group had a local recurrence or distant metastasis,resulting in a signifi cant difference(P < 0.05).In the triple-negative group and non-triple-negative group,5-year DFS were 78.9% and 87.3% respectively.There was a statistically signifi cant difference between the 2 groups(P = 0.031).CONCLUSION Compared with non-triple-negative breast cancer,triple-negative breast cancer patients have an increased likehood of a local recurrence or distant metastasis and a poorer prognosis.展开更多
Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer c...Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs) by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-II, the processed form of LC3-I, was increased. Treatment with the autophagy inhibitor, 3-methyladenine (3-MA), significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis-and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.展开更多
文摘Objective: By observing the treatment and nursing care of a patient with Grade IV capsular contracture following breast cancer expander implantation and subsequent Stage II reconstruction, we aim to analyze the reasons for the formation of capsular contracture after Stage I expander implantation and prevent its recurrence following Stage II reconstruction. Methods: In May 2020, the patient noticed an increase in the size of a breast mass. In August, she underwent AC-THP neoadjuvant chemotherapy, followed by a “right breast-conserving nipple-areolar subglandular excision + right axillary lymph node dissection + expander implantation” surgery in November 2020. Radiation therapy began in January 2021. During radiation therapy, the patient experienced severe breast hardening, distortion, tenderness, and was diagnosed with Grade IV capsular contracture. To relieve the capsular contracture, the patient underwent a “contracted capsule incision and release procedure + removal of the right breast expander + right breast implantation” surgery in July 2021. Postoperatively, measures were taken to prevent incision infection, emphasizing aseptic techniques, ensuring smooth negative pressure drainage, reducing skin flap tension, monitoring skin flap blood supply, actively preventing subcutaneous effusion and hematoma, and applying appropriate compression dressings. Results: The patient was discharged after the removal of the drainage tube. During the postoperative follow-up at 3 and 6 months, there was no recurrence of capsular contracture, and the breast appeared full, upright, and relatively soft. There were no complications such as hematoma, infection, breast implant rupture, breast sagging, or displacement. The patient had a good outcome without additional financial or surgical burdens. Conclusion: The occurrence of Grade IV capsular contracture in the patient is generally related to infection after Stage I expander implantation, improper compression dressing, excessive saline injection causing content infiltration, and radiation therapy. Therefore, it is recommended to enhance the intraoperative and postoperative prophylactic use of antibiotics after Stage I expander implantation. Intermittent saline injection after surgery, with the amount of saline gradually increasing rather than filling all at once, is advisable. This helps the breast tissue gradually adapt to expansion, reducing the risk of capsular contracture. Postoperatively, patients should be instructed to wear pressure garments and breast elastic bandages while intensifying breast monitoring during radiation therapy and increasing postoperative follow-up.
基金supported by National Natural Science Foundation of China(No.30872955)
文摘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-5p, 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 10 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 ki-67 and negatively correlated with p53 status.
基金partly supported by grants from the Chinese National Major Project for New Drug Innovation(No.2015ZX09101005)the Shenzhen municipal science and technology project(No.JCYJ20120618162903087 and No.JSGG20140515161400837)
文摘Objective: The recurrence or progression under endocrine therapy in hormone receptor-positive(HR+)advanced breast cancer(ABC) remained a critical clinical challenge.Chidamide is an oral subtype-selective histone deacetylase(HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming.The purpose of this study was to evaluate the safety,pharmacokinetics(PK),and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients.Methods: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy.Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis.In combination treatment,patients were given exemestane 25mg daily and chidamide 30mg twice a week(BIW) until progression of disease or intolerable toxicities.A treatment cycle was defined as 4 weeks.Safety,PK parameters,and preliminary efficacy were evaluated.Results: A total of 20 patients were enrolled between July and December,2015.The median number of treatments cycle was 5.2(20.8 weeks) with 2 patients still on treatment at the data cut-off date of October,2017.The treatment-related adverse events(AE) ≥ grade 3 in more than 2 patients were neutropenia(35%),thrombocytopenia(30%),and leucopenia(20%).The plasma exposure of exemestane was consistent in the presence or absence of chidamide.A slight increase in chidamide exposure was noted in the presence of exemestane,probably due to the inter-and intra-patient variations.The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors(RECIST),including 4 patients with partial response,10 patients with stable disease.The median progression-free survival(PFS) was 7.6 months.Conclusions: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients.The overall results from this study encourage further pivotal trial in this patient population.
文摘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.
基金supported by the National Natural Science Foundation of China(No.30930038)National"973"Program of China(No.2009CB521700+1 种基金2009CB918903)Program for Changjiang Scholars and Innovative Research Team in University(No.IRT0743)
文摘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.
基金supported by the Tianjin Natural Science Foundation of China (Grant No.11JCZDJC28000)
文摘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.
基金supported by the department of pathology and the PET/CT center of Affiliated Hospital of Academy of Military Medical Sciences
文摘Breast cancer is one of the most common malignancies in women.The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality.In this study,we tried to explore the role of circulating tumor cell(CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer;meanwhile,we attempted to assess the concept of "biological complete remission"(bCR) in this regard.A 56-year-old patient with breast cancer(T2N1M1,stage IV left breast cancer,with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab.Then,she underwent CTC detection and PET/CT for efficacy evaluation.CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer.The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological(pathological) complete remission.The integrated application of the concepts including bCR,imageological CR,and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.
文摘AIM To investigate the survival impact of clinicopathological factors, including pathological complete response(p CR) and tumor-infiltrating lymphocytes(s TIL) levels according to subtypes, in breast cancer(BC) patients who received neo-adjuvant chemotherapy(NAC).METHODS We evaluated 435 BC patients who presented and received NAC at the Instituto Nacional de Enfermedades Neoplasicas from 2003 to 2014. s TIL was analyzed as the proportion of tumor stroma occupied by lymphocytes, and was prospectively evaluated on hematoxylin and eosin-stained sections of the preN AC core biopsy. p CR was considered in the absence of infiltrating cancer cells in primary tumor and axillary lymph nodes. Analysis of statistical association between clinical pathological features, s TIL, p CR and survival were carried out using SPSSvs19.RESULTS Median age was 49 years(range 24-84 years) and the most frequent clinical stage was ⅢB(58.3%). Luminal A, Luminal B, HER2-enriched and(triple-negative) TN phenotype was found in 24.6%, 37.9%, 17.7% and 19.8%, respectively. p CR was observed in 11% and median percentage of s TIL was 40%(2%-95%) in the whole population. p CR was associated to Ct1-2(P = 0.045) and to high s TIL(P = 0.029) in the whole population. There was a slight trend towards significance for s TIL(P = 0.054) in Luminal A. s TIL was associated with grade Ⅲ(P < 0.001), no-Luminal A subtype(P < 0.001), RE-negative(P < 0.001), PgR-negative(P < 0.001), HER2-positive(P = 0.002) and p CR(P = 0.029) in the whole population. Longer disease-free survival was associated with grade Ⅰ-Ⅱ(P = 0.006), cN 0(P < 0.001), clinical stage Ⅱ(P = 0.004), ER-positive(P < 0.001), Pg R-positive(P < 0.001), luminal A(P < 0.001) and p CR(P = 0.002). Longer disease-free survival was associated with grade Ⅰ-Ⅱ in Luminal A(P < 0.001), N0-1 in Luminal A(P = 0.045) and TNBC(P = 0.01), clinical stage Ⅱ in Luminal A(P = 0.003) and TNBC(P = 0.038), and pC R in TNBC(P < 0.001). Longer overall survival was associated with grade Ⅰ-Ⅱ(P < 0.001), ER-positive(P < 0.001), PgR-positive(P < 0.001), Luminal A(P < 0.001), cN 0(P = 0.002) and p CR(P = 0.002) in the whole population. Overall survival was associated with clinical stage Ⅱ(P = 0.017) in Luminal A, older age(P = 0.042) in Luminal B, and pC R in TNBC(P = 0.005).CONCLUSION Predictive and prognostic values of clinicopathological features, like p CR and s TIL, differ depending on the evaluated molecular subtype.
文摘A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.
基金supported by the Chinese National Natural Sciences Foundation (No. 81672623 and No. 81502306)
文摘Objective: The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone receptor-positive early breast cancer.Methods: A retrospective analysis of 327 patients aged ≥65 years, with stage I-II, hormone receptor-positive breast cancer who underwent breast-conserving surgery and received endocrine therapy(ET) or radiotherapy plus endocrine therapy(ET+RT) was performed. Both groups were divided into luminal A type and luminal B type subgroups. Evaluation criteria were 5-year disease-free survival(DFS), local relapse rate(LRR), overall survival(OS), and distant metastasis rate(DMR).Results: There were significant differences in 5-year DFS [hazard ratio(HR)=1.59, 95% confidence interval(95% CI), 1.15-2.19;P=0.005] and LRR(HR=3.33, 95% CI, 1.51-7.34;P=0.003), whereas there were no significant differences in OS and DMR between ET group and ET+RT group. In luminal A type, there was no significant difference in 5-year DFS, LRR, OS and DMR between ET group and ET+RT group. In luminal B type,there were statistically significant differences in 5-year DFS(HR=2.19, 95% CI, 1.37-3.49;P=0.001), LRR(HR=5.45, 95% CI, 1.65-17.98;P=0.005), and OS(HR=1.75, 95% CI, 1.01-3.05;P=0.048) between ET group and ET+RT group. In the ET group, there were significant differences between luminal A type and luminal B type in5-year DFS(HR=1.84, 95% CI, 1.23-2.75;P=0.003) and OS(HR=1.76, 95% CI, 1.07-2.91;P=0.026).Conclusions: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly patients, whereas luminal A type elderly patients do not benefit from radiotherapy.Without radiotherapy, luminal A type patients have better DFS and OS than luminal B type patients.
基金supported by the National Natural Science Foundation of China （Grant No.81172532） the Program for Changjiang Scholars and Innovative Research Team in University （Grant No.TRT0743）
文摘Breast metastasis from extra-mammary malignancy is rare. An incidence of 0.4% to 1.3% has been reported in literature. The primary malignancies that most commonly metastasize to the breast are leukemia, lymphoma, and malignant melanoma. In this report, two cases of pulmonary metastasis to the breast were presented. A 40-year-old female manifested a right breast mass of 2-month duration. After physical examination was performed, a poorly defined mass was noted in the upper outer quadrant of the right breast. Another 49-year-old female manifested right breast mass of 5-day duration. A poorly defined mass was noted in the lower inner quadrant of the right breast. Mammography results also revealed breast cancer. The patients underwent local excision. After histological and immunohistochemical analyses were conducted, a primary lung carcinoma that metastasized to the breast was diagnosed. An accurate differentiation of metastasis to the breast from primary breast cancer is very important because the treatment and prognosis of the two differ significantly.
基金supported by the Special Fund of Development of Technology by Guangdong Province (No.2016A030313768)the Special Fund of Guangzhou Science and Technology Bureau (No.201707010418)+1 种基金the National Natural Science Foundation of China (No.81602645)the Science and Technology Project of Guangdong Province (No.2012A03040001)
文摘Objective:Although circulating tumor cells(CTCs)have been well-established as promising prognostic biomarkers in both early breast cancer and metastatic settings,little is known regarding the prognostic relevance of CTCs in the long-term postoperative monitoring of patients with non-metastatic breast cancer(non-MBC).In this study,we investigated the associations of CTCs with clinicopathological features and metabolic-related variables,such as obesity and hyperglycemia.Methods:In this retrospective study,we recruited 264 patients with postoperative stage Ⅰ–Ⅲ breast cancer at Guangdong General Hospital from January 2009 to December 2015.The prevalence and number of CTCs were assessed using the Cell Search System at a median time of 19.0 months[interquartile range(IQR),7.8–33.0]after surgery.The CTC assay results were correlated with the clinicopathological features and metabolic-related variables.A multivariate logistic regression analysis was performed to further determine the independent predictors of CTCs.Results:CTCs were detected in 10.6%of all patients.The positive rate of CTCs in patients with infiltrating ductal carcinoma was lower than that in patients with other pathological types(9.0%vs.28.6%,P=0.020).More importantly,the presence of CTCs was correlated with blood glucose level(P=0.015)and high-density lipoprotein level(P=0.030).The multivariate logistic regression analysis showed that the pathological type[odds ratio(OR):1.757,95%CI:1.021–3.023;P=0.042]and blood glucose level(OR:1.218,95%CI:1.014–1.465;P=0.035)were independent predictors of the presence of CTCs.Conclusions:This study revealed potential associations between CTCs and metabolic-related factors in Chinese patients with non-MBC and supports the hypothesis that metabolic dysfunction in breast cancer patients might influence the biological activity of metastatic breast cancer,leading to a higher prevalence of CTCs.
基金supported by the National Natural Science Foundation of China(Grant No.81502309)。
文摘Objective:The aim of the study was to identify specific chemosensitivity drugs for various molecular subtypes of breast tumors in Chinese women,by detecting the expression of drug resistance genes and by using the drug sensitivity test on different molecular subtypes of breast cancers.Methods:The expression of drug resistance genes including Topo Ⅱ,GST-π,P-gp,LRP,and CD133 were detected with immunohistochemistry in a tissue microarray.Drug sensitivity tests included those for paclitaxel,epirubicin,carboplatin,vinorelbine,and fluorouracil and were conducted on primary cancer tissue cells and cell lines,including the T47 D,BT-474,and MDA-MB-231 cells and human breast cancer xenografts in nude mice.Results:The different drug resistant genes Topo Ⅱ,GST-π,P-gp,and LRP were differentially expressed among different molecular subtypes of breast cancers(P<0.05).Positive expression of CD133 was highest in basal-like breast cancer(P<0.05).Kaplan-Meier survival analysis showed that positive expressions of Topo Ⅱ and CD133 both correlated with shorter disease-free survival(DFS)(P<0.05)and overall survival(P<0.05),and positive expression of LRP correlated only with shorter DFS(P<0.05).BT-474 showed chemosensitivity to paclitaxel and epirubicin,while MDA-MB-231 showed chemosensitivities to paclitaxel,epirubicin,carboplatin,and fluorouracil(T/C≤50%).The basal-like and HER2+breast cancer primary cells showed chemosensitivities to paclitaxel and epirubicin with significant differences compared with luminal breast cancer primary cells(P<0.05).Conclusions:The differential expression of drug resistance genes and the differential chemosensitivities of drugs in different molecular subtype of breast cancers suggested that individual treatment should be given for each type of breast cancer.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.82072588,82002601,81872143,and 81702280)the National Science and Technology Support Program of China(Grant Nos.2015BAI12B15 and 2018ZX09201015)+2 种基金the National Key Research and Development Program of Chinathe Net Construction of Human Genetic Resource Bio-bank in North China(2016YFC1201703),the Projects of Science and Technology of Tianjin(Grant Nos.13ZCZCSY20300 and 18JCQNJC82700)the Key Project of Tianjin Health and Family Planning Commission(Grant No.16KG126).
文摘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.
文摘In this work, patterned macropores with a diameter larger than 100 μm were introduced to pristine three-dimensional (3D) nanofibrous bacterial cellulose (BC) scaffolds by using the infrared laser micromachining technique in an attempt to create an in vitro model for the culture of breast cancer cells. The morphology, pore structure, and mechanical performance of the obtained patterned macroporous BC (PM-BC) scaffolds were characterized by scanning electron microscopy (SEM), mercury intrusion porosimeter, and mechanical testing. A human breast cancer cell (MDA-MB-231) line was cultured onto the PM-BC scaffolds to investigate the role of macropores in the control of cancer cell behavior. MTT assay, SEM, and hematoxylin and eosin (H&E) staining were employed to determine cell adhesion, growth, proliferation, and infiltration. The PM-BC scaffolds were found to be able to promote cellular adhesion and proliferation on the scaffolds, and further to allow for cell infiltration into the PM-BC scaffolds. The results demonstrated that BC scaffolds with laser-patterned macropores were promising for the in vitro 3D culture of breast cancer cells.
文摘Reports of BRCA2 genetic mutations on the prognosis of familial breast cancer(BC) patients have been contradictory. True difference in survival,if it exists,would have important implications for genetic counseling and in treatment of hereditary BC. The purpose of this study was to compare overall survival rate(OSR) among BRCA2 mutation carriers,non-carriers and sporadic BC patients. We searched the PUBMED and EMBASE databases and retrieved 4529 articles using keywords that included breast cancer,BRCA,prognosis and survival. Nine articles were selected for systematic review and among them 6 were included in our meta-analysis. We used the fixed and random effect models to calculate the summary odds ratio(OR) and corresponding 95% confidence interval(CI). BRCA2 mutation carriers had significantly higher long-term OSR than non-carriers(OR=0.69 [95% CI=0.5–0.95]),while both short-term and long-term OSR of BRCA2 mutation carriers did not differ from those of patients with sporadic disease(OR=1.11 [95% CI=0.74–1.65]; 0.85 [95% CI=0.38–1.94],respectively). For BC-specific survival rate(BCSSR),BRCA2 mutation carriers had a similar BCSSR to the non-carriers(OR=0.61 [95% CI=0.28–1.34]). There was no significant difference in disease-free survival(DFS) between BRCA2 mutation carriers and patients with sporadic disease. Our results suggest that BRCA2 mutation increases long-term OSR in hereditary BC,which reminds us a new prospect of management of the disease.
基金supported by grant from the CAMS Innovation Fund for Medical Sciences (CIFMS, No. 2021I2M-1-014)。
文摘Objective: The mechanism of acquired gene mutation plays a major role in resistance to endocrine therapy in hormone receptor(HR)-positive advanced breast cancer. Circulating tumor DNA(ctDNA) has been allowed for the assessment of the genomic profiles of patients with advanced cancer. We performed this study to search for molecular markers of endocrine therapy efficacy and to explore the clinical value of ctDNA to guide precise endocrine therapy for HR-positive/human epidermal growth factor receptor-2(HER-2)-negative metastatic breast cancer patients.Methods: In this open-label, multicohort, prospective study, patients were assigned to four parallel cohorts and matched according to mutations identified in ctDNA: 1) activation of the phosphatidylinositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR) signaling pathway preferred mTOR inhibitor combined with endocrine therapy;2) estrogen receptor 1(ESR1) mutation preferred fulvestrant;3) HER-2 mutations preferred pyrotinib;and 4) no actionable mutations received treatment according to the clinical situation. In all cohorts, patients were divided into compliance group and violation group. The primary outcome measure was progression-free survival(PFS), and the secondary outcome measure was overall survival(OS).Results: In all cohorts, the combined median PFS was 4.9 months, and median PFS for the compliance and violation groups was 6.0 and 3.0 months, respectively [P=0.022, hazard ratio(HR)=0.57]. Multivariate Cox regression model showed the risk of disease progression was lower in compliance group than in violation group(P=0.023, HR=0.55). Among the patients with HER-2 mutations, the median PFS was 11.1 months in the compliance group and 2.2 months in the violation group(P=0.011, HR=0.20). There was no significant difference in the median PFS between patients who did and did not comply with the treatment protocol in patients with activation of the PI3K/AKT/mTOR or ESR1 mutation.Conclusions: The results suggest that ctDNA may help to guide the optimal endocrine therapy strategy for metastatic breast cancer patients and to achieve a better PFS. Next-generation sequencing(NGS) detection could aid in distinguishing patients with HER-2 mutation and developing new treatment strategies.
基金a grant from Science and Technology Planning Project of Tanjin,China(No.043111111)
文摘OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 treated in the Cancer Hospital of Tianjin Medical University were analyzed.The Her-2,ER and PR status was determined using immunohistochemistry.Of the total cases,one group was identifi ed as triple negative breast cancer,ie defi ned as ER,PR and Her-2 negative.The other group was non-triple-negative breast cancer.Clinicopathologic features of the groups were compared and 5-year disease-free survival(DFS) analyzed by the Kaplan-Meier method.RESULTS Of the total cases,21.4%(109/509) of cases were found to be triple-negative while 78.6%(400/509) were non-triple-negative.The triple negative group had higher incidence rates than the non-triple-negative group of the medullary type and Grade Ⅲ tumors(P < 0.05).There was no other difference in the clinicopathologic features between the 2 groups.From follow-up to June,2007,21.1%(23/109) of the triple-negative group and 12.7%(51/400) of the non-triple negative group had a local recurrence or distant metastasis,resulting in a signifi cant difference(P < 0.05).In the triple-negative group and non-triple-negative group,5-year DFS were 78.9% and 87.3% respectively.There was a statistically signifi cant difference between the 2 groups(P = 0.031).CONCLUSION Compared with non-triple-negative breast cancer,triple-negative breast cancer patients have an increased likehood of a local recurrence or distant metastasis and a poorer prognosis.
基金supported by the National Natural Science Foundation of China (Grant no. 81001186)the Tianjin Municipal Natural Science Foundation (Grant no. 10JCYBJ C14100,11JCZDJC28000,13JCYBJC21800)
文摘Apigenin (4',5,7-trihydroxyflavone) is a member of the flavone subclass of flavonoids present in fruits and vegetables. The involvement of autophagy in the apigenin-induced apoptotic death of human breast cancer cells was investigated. Cell proliferation and viability were assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenic assays. Flow cytometry, fluorescent staining and Western blot analysis were employed to detect apoptosis and autophagy, and the role of autophagy was assessed using autophagy inhibitors. Apigenin dose- and time-dependently repressed the proliferation and clonogenic survival of the human breast cancer T47D and MDA-MB-231 cell lines. The death of T47D and MDA-MB-231 cells was due to apoptosis associated with increased levels of Caspase3, PARP cleavage and Bax/Bcl-2 ratios. The results from flow cytometry and fluorescent staining also verified the occurrence of apoptosis. In addition, the apigenin-treated cells exhibited autophagy, as characterized by the appearance of autophagosomes under fluorescence microscopy and the accumulation of acidic vesicular organelles (AVOs) by flow cytometry. Furthermore, the results of the Western blot analysis revealed that the level of LC3-II, the processed form of LC3-I, was increased. Treatment with the autophagy inhibitor, 3-methyladenine (3-MA), significantly enhanced the apoptosis induced by apigenin, which was accompanied by an increase in the level of PARP cleavage. Similar results were also confirmed by flow cytometry and fluorescence microscopy. These results indicate that apigenin has apoptosis-and autophagy-inducing effects in breast cancer cells. Autophagy plays a cyto-protective role in apigenin-induced apoptosis, and the combination of apigenin and an autophagy inhibitor may be a promising strategy for breast cancer control.
