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Modern Pathology : An Official Journal... Aug 2022Metaplastic breast carcinomas are a rare and heterogeneous group of tumors (0.5-2%). They are mainly triple negative tumors but they present poorer chemotherapy...
Metaplastic breast carcinomas are a rare and heterogeneous group of tumors (0.5-2%). They are mainly triple negative tumors but they present poorer chemotherapy responses and worse prognosis than other triple negative tumors. The aim of our study was to characterize the molecular profile and tumor evolution in matched (primary-relapse) tumor samples from patients with early-stage metaplastic breast carcinomas who had disease recurrence/progression. We performed genomic profiling of tumor biopsies at least from two different time points of their tumor evolution. Tumor samples were analyzed by DNA-Next Generation Sequencing (Illumina 2 x 75bp) using the Action OncoKitDX panel (Imegen-Health in Code group), which includes point mutations in 50 genes, CNVs, and fusion genes. Only pathogenic and likely pathogenic variants were considered for analysis and they were categorized following the ComPerMed criteria. We analyzed 21 matched tumor samples (8 primary and 13 relapse/progression samples). Genomic profiling of matched tumor samples revealed that mutations present in primary tumors are generally maintained in the relapse/disease progression. We did not find a significant increase in point mutations between primary and relapse/progression samples, although gene amplifications were found more frequently in relapse/progression samples. Tumor samples harbored high frequency of TP53 (100%) and TERT promoter (29%) mutations, and of MYC amplifications (80% of which in relapse/progression samples). No PI3KCA mutations were found, but PTEN variations were enriched in 38% of samples (10% mutations and 28% deletions). FGFR1 amplifications were identified in 13% of samples (primary tumor only). Neither ERBB2 nor EGFR gene amplifications were detected. The most frequent pathogenic alterations occurred in cycle regulation's genes, including TP53 and TERT promoter mutations, and MYC amplifications. Relapse/progression samples were highly enriched for MYC amplification. Larger studies are required to better characterize these tumors, and identify new strategies to improve the prognosis of these patients.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Gene Amplification; Genomics; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasm Recurrence, Local
PubMed: 35177782
DOI: 10.1038/s41379-022-01017-7 -
Clinical Breast Cancer Aug 2017We aimed to describe our experience with metaplastic breast carcinoma (MBC), evaluate its clinical outcome compared with triple-negative breast cancer (TNBC), and... (Comparative Study)
Comparative Study Review
BACKGROUND
We aimed to describe our experience with metaplastic breast carcinoma (MBC), evaluate its clinical outcome compared with triple-negative breast cancer (TNBC), and provide a through and comprehensive review of the literature to date.
MATERIALS AND METHODS
We reviewed MBC cases (n = 46) from our institution. The following variables were recorded: tumor histologic subtype, Nottingham grade, tumor size, lymph node status, Tumor, Node, Metastases stage, biomarkers profile, patient's age and race, therapy modality (chemotherapy and radiation), and survival (disease-free survival [DFS] and overall survival [OS]). The clinical and pathological data for TNBC (n = 508) cases were extracted from the breast cancer database. To compare the survival between MBC and TNBC, a subgroup of MBC cases (n = 40) were matched with TNBC cases (n = 40) on the basis of known prognostic confounders.
RESULTS
There were 17 of 46 (37%) cases with mesenchymal differentiation, 12 (26.1%) squamous cell carcinoma, 14 (30.4%) spindle cell carcinoma, and 3 (6.5%) mixed type. MBC presented at a more advanced stage than TNBC (P = .014) and was more likely to recur (34% vs. 15.5%; P = .004). More MBC patients died from disease than TNBC (29% vs. 16%; P = .05). In the multivariate analysis, MBC had approximately twice the risk of local recurrence than TNBC (95% confidence interval, 1.01-3.83; P = .05). MBC patients had worse DFS and OS than the matched TNBC patients (P < .001 and P = .033, respectively). A review of the literature comparing MBC versus TNBC is presented.
CONCLUSION
Our results suggest that MBC is clinically more aggressive than TNBC. Further studies might help delineate the differences between these 2 entities.
Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Ductal, Breast; Carcinoma, Squamous Cell; Female; Humans; Metaplasia; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Survival Rate; Triple Negative Breast Neoplasms
PubMed: 28529029
DOI: 10.1016/j.clbc.2017.04.009 -
Oncology Letters Nov 2016Metaplastic carcinoma of the breast is a rare form of breast cancer. The aim of the present study was to investigate the imaging and pathological features of metaplastic...
Metaplastic carcinoma of the breast is a rare form of breast cancer. The aim of the present study was to investigate the imaging and pathological features of metaplastic carcinoma. The features identified on mammography and sonography were retrospectively reviewed in 13 women with metaplastic carcinoma of the breast. The results from the mammographs and sonographs were additionally evaluated using immunohistochemical staining for the expression of the estrogen receptor (ER) and progesterone receptor (PR), receptor tyrosine-protein kinase erbB-2 (CerbB-2) and P53. The most common features observed in the mammographs were as follows: Irregular and oval shaped masses, 53.8 and 46.2%, respectively; spiculated and circumscribed margins, each 30.8%; and high and marginally high density masses, 69.2 and 30.8%, respectively. The most common sonography features observed were as follows: Hypoechoic masses, 84.6%; complex echogenicity, 76.9%; irregular, round and oval shaped masses, 69.2, 30.8 and 30.8%, respectively; indistinct and circumscribed margins, 53.8 and 46.2%, respectively; an abundant blood flow, 53.8%; and posterior acoustic enhancement, 61.5%. The immunohistochemical (IHC) profile for 13 patients demonstrated that ER was not expressed in 100% of patients, PR and CerbB-2 were not present in 92.3% of patients, and P53 was present in 63.6% of patients. Therefore, metaplastic carcinoma of the breast exhibits more benign IHC features compared with invasive ductal carcinoma. In addition, it may be challenging to diagnose patients that do not possess posterior acoustic enhancement or express hormone receptors from other types of breast cancer.
PubMed: 27895758
DOI: 10.3892/ol.2016.5177 -
Transactions of the American Clinical... 2019Gastrointestinal cancers are largely epithelial in nature and arise from the esophagus, stomach, pancreas, colorectum and liver. In aggregate, these cancers are the most...
Gastrointestinal cancers are largely epithelial in nature and arise from the esophagus, stomach, pancreas, colorectum and liver. In aggregate, these cancers are the most common malignancies in the United States and worldwide, but suffer from poor outcomes in late stages. Our overall work aims to elucidate the following: 1) how normal epithelial cells become metaplastic and dysplastic; 2) how tumor cells invade and interact with activated fibroblasts and immune cells; and 3) how tumor cells disseminate into the circulation and colonize distant organs (metastatic organotropism). We develop three-dimensional cell culture models and genetically engineered mouse models to decipher mechanisms. Our overarching desire is to translate preclinical models to clinical trials that impact upon outcomes in patients with metastatic gastrointestinal cancers. We will frame these principles and approaches in the context of esophageal cancers and three-dimensional models.
Topics: Adenocarcinoma; Animals; Animals, Genetically Modified; Disease Models, Animal; Epithelial Cells; Esophageal Mucosa; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagus; Humans; Organoids; Tissue Culture Techniques
PubMed: 31516191
DOI: No ID Found -
Cancers Jul 2020Metaplastic breast carcinoma (MBC) is a heterogeneous group of infrequent invasive carcinomas that display differentiation of the neoplastic epithelium towards squamous... (Review)
Review
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 and . Additionally, mutations in the other genes of the PI3K/AKT pathway indicated its importance in the pathogenesis of MBC. Regarding copy number variations (CNVs), was the most frequently amplified gene, and the most frequent gene loss affected the 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.
PubMed: 32650408
DOI: 10.3390/cancers12071832 -
Cancer Treatment and Research... 2022Metaplastic breast carcinoma (MBC) is a rare histologic variant of breast cancer characterized by the presence of glandular and non-glandular components. The prognostic... (Review)
Review
BACKGROUND
Metaplastic breast carcinoma (MBC) is a rare histologic variant of breast cancer characterized by the presence of glandular and non-glandular components. The prognostic significance of estrogen receptor (ER) status has been scarcely studied in these tumors. We therefore investigated the prognostic relevance of ER status in MBC within our patient population.
DESIGN
We reviewed MBC cases (n = 125) between January 2000 and September 2019. Histologic slides were reviewed for variables including tumor morphology and hormonal status. Additional clinical information was obtained from the electronic medical records.
RESULTS
Of the 125 patients, 15 (12%) had ER positive tumors and 110 (88%) had ER negative tumors. Eleven (73%) ER positive tumors had ER positivity > 10% and 4 (27%) had ER positivity ≤ 10%. ER positive tumors had a smaller median tumor size of 2.5 cm, compared with ER negative tumors with median tumor size 3.05 cm, however this difference was not statistically significant (P = 0.82). There were no statistical differences between ER positive and ER negative tumors in terms of histologic grade (P = 0.34), histologic subtype (P = 0.65), clinical stage (P>0.99) or human epidermal growth factor receptor 2 (HER2) expression (P = 0.29). There was also no difference in overall survival (OS) between ER positive and ER negative metaplastic breast cancers (HR = 0.35, 95% CI, 0.003-2.67, P = 0.39).
CONCLUSION
Our experience suggests that ER positivity has no prognostic relevance in MBC. Regardless of ER expression status, there were no statistically significant differences in overall survival between ER positive and ER negative MBC.
Topics: Humans; Female; Receptors, Estrogen; Breast Neoplasms; Prognosis; Metaplasia
PubMed: 36058202
DOI: 10.1016/j.ctarc.2022.100630 -
Molecular and Clinical Oncology Sep 2021Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the...
Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.
PubMed: 34276997
DOI: 10.3892/mco.2021.2340 -
Diagnostic and Interventional Radiology... Jan 2023Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer characterized by mixed epithelial and mesenchymal differentiation. Commonly seen subtypes...
Metaplastic breast cancer (MBC) is a rare subtype of invasive breast cancer characterized by mixed epithelial and mesenchymal differentiation. Commonly seen subtypes include squamous cell carcinoma, spindle cell carcinoma, and metaplastic carcinoma with heterologous mesenchymal differentiation. MBC tends to have a more aggressive clinical presentation, higher metastatic potential, higher rates of local recurrence, and a worse prognosis compared with invasive breast carcinoma of no special type. Most MBCs are triple-negative breast cancers, which explains their resistance to most systemic therapies. Therefore, accurately diagnosing MBC early is crucial for deciding the treatment strategy and predicting the prognosis. In this pictorial essay, the imaging findings of MBC in different modalities and the histopathologic features of its subtypes are reviewed.
Topics: Humans; Female; Breast Neoplasms; Carcinoma, Ductal, Breast; Triple Negative Breast Neoplasms; Multimodal Imaging; Prognosis
PubMed: 36959869
DOI: 10.4274/dir.2022.221363 -
Gastrointestinal Endoscopy Clinics of... Jan 2021Barrett's esophagus is the precursor lesion for esophageal adenocarcinoma. The goals of endoscopic surveillance are to detect dysplasia and early esophageal... (Review)
Review
Barrett's esophagus is the precursor lesion for esophageal adenocarcinoma. The goals of endoscopic surveillance are to detect dysplasia and early esophageal adenocarcinoma in order to improve patient outcomes. Despite the ongoing debate regarding the efficacy of surveillance, all current gastrointestinal societies recommend surveillance at this time. Optimal surveillance technique includes adequate inspection time, evaluation using high-definition white light and chromoendoscopy, appropriate documentation of the metaplastic segment using the Prague C & M criteria as well as the Paris classification should lesions be found, utilization of the Seattle biopsy protocol, and endoscopic resection of visible lesions.
Topics: Adenocarcinoma; Barrett Esophagus; Biopsy; Early Detection of Cancer; Endoscopic Mucosal Resection; Esophageal Neoplasms; Esophagoscopy; Esophagus; Humans; Population Surveillance; Practice Guidelines as Topic; Precancerous Conditions
PubMed: 33213800
DOI: 10.1016/j.giec.2020.08.003 -
Head and Neck Pathology Mar 2020This manuscript provides an overview of pleomorphic spindle cell tumors presenting on sun-damaged skin of the elderly and includes discussions of atypical fibroxanthoma,... (Review)
Review
This manuscript provides an overview of pleomorphic spindle cell tumors presenting on sun-damaged skin of the elderly and includes discussions of atypical fibroxanthoma, pleomorphic dermal sarcoma, spindle cell and metaplastic squamous cell carcinoma, spindle cell and dedifferentiated melanoma and poorly differentiated cutaneous angiosarcoma. These tumors share many of the clinical presenting and histological features, making confident diagnosis challenging. A reliable and robust diagnosis is necessary to predict behavior as the biologic potential of these tumors ranges from benign (e.g. atypical fibroxanthoma) to outright malignant with poor survival rates (e.g. cutaneous angiosarcoma). The salient clinical, histologic and immunohistochemical characteristics are discussed in detail with emphasis on distinguishing features and differential diagnosis to provide the reader with a better understanding of these entities and helpful clues for a more robust diagnosis.
Topics: Carcinoma, Squamous Cell; Fibroma; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Melanoma; Sarcoma; Skin Neoplasms
PubMed: 31950467
DOI: 10.1007/s12105-019-01084-4