Clinicopathological characteristics and prognosis of metaplastic carcinoma of the breast.
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ABSTRACT:
SUBMITTER: Xiao M
PROVIDER: S-EPMC5530147 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:BackgroundSpindle cell carcinoma (SpCC) of the breast is a rare histological type, a subtype of metaplastic carcinoma characterized by atypical spindle cell and epithelial carcinoma. The proportions of the spindle cell and epithelial components vary among tumours. Due to its rarity, biological characteristics of this disease have been poorly studied.MethodsIn total, 10 patients with SpCC were surgically treated at our institution from January 2007 to December 2018. We retrospectively investigated these SpCC cases, focusing on the differences between spindle cell and epithelial components. Microsatellite status was also examined.ResultsNine cases were triple-negative breast cancer (TNBC). The rates of high tumour grade were 70% in spindle cell components and 56% in epithelial components (P = .65), while the mean Ki67 labelling index were 63% and 58%, respectively (P = .71). Mean programmed death ligand 1 (PD-L1) expression in these components was 11% and 1%, respectively (P = .20). All 10 tumours were microsatellite stable. Patient outcomes of triple-negative SpCC did not differ from those of propensity-matched patients with conventional TNBC.ConclusionsSpindle cell components showed higher values in factors examined, although there was no statistically significant difference. Our data reveal that these 2 components of SpCC may be of different biological nature.
| S-EPMC8369969 | biostudies-literature
Project description:BackgroundTo better understand the clinicopathological features and prognostic profiles of squamous cell carcinoma (SCC) of the breast.MethodsInformation on breast cancer was obtained from the Surveillance, Epidemiology, and End Results database (2004-2016). Comparative analyses were carried out to investigate the heterogeneity in the clinicopathological characteristics and survival outcomes between SCC and invasive ductal carcinoma (IDC), while propensity score matching was conducted to analyze the variations among baseline characteristics. Prognostic factors for SCC of the breast were successively identified using Cox regression analysis.ResultsA total of 382 SCC patients and 561477 IDC patients were identified in this study. Comparatively, the SCC cohort exhibited a higher proportion of male individuals, poor differentiation, an advanced TNM stage, an increasing percentage of triple-negative (TN) subtype, an increasing rate of organ involvement, and less access to therapeutics. The aggressive profile was consistent in the TN subgroup, with a significantly higher proportion in SCC than in IDC (25.7% vs 6.8%). Prognosis of SCC was profoundly poorer than that of IDC (mOS, 78.6 months and 121.6 months, P < .0001; mBCSS 91.9 months vs 135.6 months, P < .0001), of which the inferior tendency remained stable among disease stage and therapeutic options, while no difference was detected in the 2 subgroups with the TN subtype. The 2-year survival rate was 66.9% and the 5-year survival rate was 51.4%, with the risk factors being older age, bilateral disease, advanced TNM stage, bone and visceral involvement, surgical intervention, radiation treatment, and chemotherapy.ConclusionsThis study systematically analyzed the heterogeneous characteristics of SCC of the breast in comparison with IDC. Squamous cell breast cancer presented with increasing aggressive behavior and inferior prognosis. Prospective studies should focus on this subgroup and introduce individualized therapeutic protocols in clinical practice.
| S-EPMC8521731 | biostudies-literature
Project description:Metaplastic breast carcinoma (MBC) is a rare subtype of invasive breast cancer and has poor prognosis. In general, cancers are heterogeneous cellular masses comprised of different cell types and their extracellular matrix (ECM). However, little is known about the composition of the ECM and its constituents in MBC. Decorin is a ubiquitous ECM macromolecule known of its oncosuppressive activity. As such, it provides an intriguing molecule in the development of novel therapeutics for different malignancies such as MBC. In this study, decorin immunoreactivity and the effect of adenoviral decorin cDNA (Ad-DCN) transduction were examined in MBC. Multiple immunohistochemical stainings were used to characterize a massive breast tumour derived from an old woman. Furthermore, three-dimensional (3D) explant cultures derived from the tumour were transduced with Ad-DCN to study the effect of the transduction on the explants. The MBC tumour was shown to be completely negative for decorin immunoreactivity demonstrating that the malignant cells were not able to synthesize decorin. Ad-DCN transduction resulted in a markedly altered cytological phenotype of MBC explants by decreasing the amount of atypical cells and by inhibiting cell proliferation. The results of this study support approaches to develop new, decorin-based adjuvant therapies for MBC.
| S-EPMC5750199 | biostudies-literature
Project description:ObjectiveThe present study was designed to better characterize the clinicopathological features and prognosis in patients aged ≥65 years with pulmonary large cell neuroendocrine carcinoma (LCNEC).MethodsEligible patients with pulmonary LCNEC were retrieved from the Surveillance, Epidemiology, and End Results database between January 2004 and December 2013. The primary endpoints included cancer-specific survival (CSS) and overall survival (OS).ResultsData of 1,619 eligible patients with pulmonary LCNEC were collected. These patients were subsequently categorized into two groups: 890 patients in the older group (age ≥65 years), and 729 in the younger group (age <65 years). More patients were of white ethnicity, stage I, married, and with tumor size <5 cm in the older group in comparison to the younger group. However, there were a significantly lower proportion of patients undergoing surgery, chemotherapy, and radiotherapy in the older group. The 5-year CSS rates of the younger group and older group were 23.94% and 17.94% (P = 0.00031), respectively, and the 5-year OS rates were 20.51% and 13.47% (P < 0.0001), respectively. Multivariate analyses indicated that older age (CSS: HR 1.20, 95% CI [1.07-1.36], P = 0.0024; OS: HR 1.26, 95% CI [1.12-1.41], P < 0.0001) was an independent risk factor for poor prognosis. The mortality risk of the elderly increased in almost every subgroup, especially in OS. Finally, significant predictors for better OS and CSS in patients over age 65 included tumor size <5 cm, lower stage, and receiving surgery, chemotherapy, or radiotherapy.ConclusionThe prognosis of patients aged ≥65 years with pulmonary LCNEC was worse than that of younger patients. However, active and effective therapy could significantly improve the survival of older patients with pulmonary LCNEC.
| S-EPMC6532618 | biostudies-literature
Project description:BackgroundMetaplastic breast carcinoma (MpBC) typically consists of carcinoma of no special type (NST) with various metaplastic components. Although previous transcriptomic and proteomic studies have reported subtype-related heterogeneity, the intracase transcriptomic alterations between metaplastic components and paired NST components, which are critical for understanding the pathogenesis underlying the metaplastic processes, remain unclear.MethodsFifty-nine NST components and paired metaplastic components (spindle carcinomatous [SPS], matrix-producing, rhabdoid [RHA], and squamous carcinomatous [SQC] components) were microdissected from specimens obtained from 27 patients with MpBC for gene expression profiling using the NanoString Breast Cancer 360 Panel on a NanoString nCounter FLEX platform. BC360-defined signatures were scored using nSolver software.ResultsHierarchical clustering and principal component analysis revealed a heterogeneous gene expression profile (GEP) corresponding to the NST components, but the GEP of metaplastic components exhibited subtype dependence. Compared with the paired NST components, the SPS components demonstrated the upregulation of genes related to stem cells and epithelial-mesenchymal transition and displayed enrichment in claudin-low and macrophage signatures. Despite certain overlaps in the enriched functions and signatures between the RHA and SPS components, the specific differentially expressed genes differed. We observed the RHA-specific upregulation of genes associated with vascular endothelial growth factor signaling. The chondroid matrix-producing components demonstrated the upregulation of hypoxia-related genes and the downregulation of the immune-related MHC2 signature and the TIGIT gene. In the SQC components, TGF-β and genes associated with cell adhesion were upregulated. The differentially expressed genes among metaplastic components in the 22 MpBC cases with one or predominantly one metaplastic component clustered paired NST samples into clusters with correlation with their associated metaplastic types. These genes could be used to separate the 31 metaplastic components according to respective metaplastic types with an accuracy of 74.2%, suggesting that intrinsic signatures of NST may determine paired metaplastic type. Finally, the EMT activity and stem cell traits in the NST components were correlated with specimens displaying lymph node metastasis.ConclusionsWe presented the distinct transcriptomic alterations underlying metaplasia into specific metaplastic components in MpBCs, which contributes to the understanding of the pathogenesis underlying morphologically distinct metaplasia in MpBCs.
| S-EPMC9883935 | biostudies-literature
Project description:Various studies have evaluated the significance of PTEN (phosphatase and tensin homolog deleted from chromosome 10) expression in breast cancer, but their results remain controversial. We conducted a meta-analysis to evaluate the associations of PTEN expression with clinicopathological characteristics and prognosis in breast cancer. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to identify relevant publications. The associations between PTEN expression and clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) were then assessed via meta-analyses of odds ratio (ORs) and hazard ratio (HRs) with 95% confidence intervals (CIs). Based on 27 studies involving 10,231 patients, the pooled results revealed that PTEN loss was significantly more common in breast cancer than in normal tissues (OR = 12.15, 95% CI = 6.48-22.79, P < 0.00001) and that PTEN loss had clear associations with larger tumor size (> 2 cm, OR = 0.62, 95% CI = 0.48-0.82, P = 0.0006), lymph node metastasis(OR = 0.61, 95% CI = 0.45-0.82, P = 0.0001), later TNM stage(stage III-IV, OR = 0.55, 95% CI = 0.35-0.86, P = 0.009), poor differentiation(OR = 0.37, 95% CI = 0.24-0.59, P < 0.0001), and the highly aggressive triple-negative phenotype (OR = 1.62, 95% CI = 1.23-2.12, P = 0.0005). Moreover, patients with PTEN loss exhibited significantly worse DFS and OS(HR = 1.63, 95% CI = 1.04-2.22, P < 0.00001; HR = 1.41, 95% CI = 1.08-1.73, P < 0.0001; respectively). In conclusion, PTEN loss might predict more aggressive behavior and worse outcomes in patients with breast cancer.
| S-EPMC5458267 | biostudies-literature
Project description:BackgroundMetaplastic breast cancer (MBC) is a rare and aggressive subtype of breast. However, the effect of molecular subtype on treatment and prognosis of MBC remains unclear.Patients and methodsThe Surveillance, Epidemiology, and End Results database was used to analyze patients with MBC between 2010 and 2016. Molecular subtype was stratified to TN group (ER and PR-/HER2-), HER2 group (ER and PR-/HER2+, ER/PR+ and HER2+), and HR group (ER/PR+ and HER2-). The breast cancer-specific survival (BCSS) differences were estimated using multivariate Cox regression model and Kaplan-Meier curves.ResultsWe included 1665 patients with median follow-up time of 27 months (range 0-83 months). 1154 (69.3%), 65 (3.9%), and 446 (26.8%) patients presented in TN group, HER2 group, and HR group, respectively. On multivariate Cox analysis, the prognosis was related to age, tumor size, regional node metastasis, and surgery. Molecular subtype remained no impact on BCSS. Radiotherapy (RT) was associated with better prognosis. Patients cannot benefit from chemotherapy. In Kaplan-Meier curve, triple-negative (P = 0.047) and HR-positive (P = 0.006) patients receiving RT had a superior BCSS than that not RT. HER2-positive patients cannot benefit from RT. However, adjusted Kaplan-Meier survival model showed that triple-negative (P = 0.019) but not HER2-positive (P = 0.575) or HR-positive (P = 0.574) patients receiving RT had a superior BCSS than that not RT.ConclusionsMolecular subtype is not associated with the better prognosis of MBC. Patients could benefit from RT. However, triple-negative but not HR-positive or HER2-positive patients have superior survival after receiving RT.
| S-EPMC8079171 | biostudies-literature
Project description:BackgroundHuman epidermal growth factor 2 (HER2)-low breast cancer, which is defined as HER2 1+ or 2+ in immunohistochemistry without gene amplification, accounts for a considerable part of all breast cancers. However, it remains controversial whether HER2-low breast cancer is a distinct entity. Our aim was to compare the clinicopathological features and survival outcomes between HER2-zero and HER2-low early breast cancer.MethodsThe study was a retrospective analysis that enrolled 1,039 patients with available HER2 expression data in a single institute from 2013 to 2014, of whom 262 HER2-positive patients were excluded from the subsequent analysis. The remaining patients were divided into HER2-zero and HER2-low groups. Each group was further categorized into a hormone receptor (HR)-positive and an HR-negative subgroup. Clinicopathological characteristics were collected and compared between HER2-zero and HER2-low groups. The primary endpoint was disease-free survival (DFS) and overall survival (OS), which were analyzed using the Kaplan-Meier method with log-rank test, landmark analysis, and Cox proportional hazards model.ResultsA total of 777 non-HER2-positive patients were included in this analysis, of whom 126, 552, 53, and 46 patients were HR-positive/HER2-zero, HR-positive/HER2-low, HR-negative/HER2-zero, and HR-negative/HER2-low, respectively. No significant difference in DFS and OS was detected between the HER2-zero group and the HER2-low group when paired by HR status. Landmark analysis with a time point set at 5 years indicated that HR-positive/HER2-low patients had a better DFS compared with HR-positive/HER2-zero patients after 5 years (p = 0.0047). HER2-low status was an independent prognostic factor for DFS after 5 years [hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.13-0.75, p = 0.01].ConclusionThe clinicopathological characteristics and prognosis of HER2-zero and HER2-low breast cancer were similar regardless of HR status. Patients with HR-positive/HER2-low tumors tended to have a better DFS than their HR-positive/HER2-zero counterparts after 5 years.
| S-EPMC9245921 | biostudies-literature
Project description:SNP6 profiling of metaplastic breast carcinoma Metaplastic breast carcinoma (MBC) is a rare and aggressive histologic type of breast cancer, preferentially displaying a triple-negative phenotype (i.e. lacking estrogen receptor, progesterone receptor and HER2 expression). We sought to define the transcriptomic heterogeneity of MBCs on the basis of current gene expression microarray-based classifiers and to determine whether MBCs display gene copy number profiles consistent with those of BRCA1-associated breast cancers.
2014-10-31 | E-GEOD-57548 | biostudies-arrayexpress
Project description:Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent invasive carcinomas that display differentiation of the neoplastic epithelium towards squamous cells and/or mesenchymal-type elements. Most MBC have a triple negative phenotype and poor prognosis. Thus, MBC have worse survival rates than other invasive breast carcinomas, including other triple negative breast carcinomas (TNBC). In this study, we reviewed the molecular features of MBC, pointing out the differences among subtypes. The most frequently mutated genes in MBC were TP53 and PIK3CA. Additionally, mutations in the other genes of the PI3K/AKT pathway indicated its importance in the pathogenesis of MBC. Regarding copy number variations (CNVs), MYC was the most frequently amplified gene, and the most frequent gene loss affected the CDKN2A/CDKN2B locus. Furthermore, the pattern of mutations and CNVs of MBC differed from those reported in other TNBC. However, the molecular profile of MBC was not homogeneous among histological subtypes, being the alterations in the PI3K pathway most frequent in spindle cell carcinomas. Transcriptomic studies have demonstrated an epithelial to mesenchymal program activation and the enrichment of stemness genes in most MBC. In addition, current studies are attempting to define the immune microenvironment of these tumors. In conclusion, due to specific molecular features, MBC have a different clinical behavior from other types of TNBC, being more resistant to standard chemotherapy. For this reason, new therapeutic approaches based on tumor molecular characteristics are needed to treat MBC.
| S-EPMC7408634 | biostudies-literature