Carcinosarcoma of the Breast: An Aggressive Subtype of Metaplastic Cancer. Report of a Rare Case in a Young BRCA-1 Mutated Woman

Ghilli, Matteo; Mariniello, Maria Donatella; Fanelli, Giovanni; Cascione, F.; Fontana, A.; Cristaudo, Agostino; Cilotti, A; Caligo, Maria A.; Manca, G; Colizzi, Livio; Naccarato, Antonio Giuseppe; Roncella, Manuela

doi:10.1016/j.clbc.2016.08.002

Cited by 16 publications

(14 citation statements)

References 22 publications

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“…MBC can carry mutations in BRCA1 (3–15%), BRCA2 (2–6%), and ATM (2–12%) ( Table S1 ). Interestingly, MBC have been occasionally reported in BRCA1 germline mutation carriers [ 44 , 45 , 46 , 47 ].…”

Section: Molecular Alterationsmentioning

confidence: 99%

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

González-Martínez

Pérez-Míes

Carretero‐Barrio

et al. 2020

Cancers

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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.

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Section: Molecular Alterationsmentioning

confidence: 99%

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

González-Martínez

Pérez-Míes

Carretero‐Barrio

et al. 2020

Cancers

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“…A recent series has reported that BRCA1/2 were found mutated in 18% and 27%, respectively of ECS [30], although in the TCGA (The Cancer Genome Atlas Program) series, only BRCA2 mutations were detected and at a lower frequency (5%) [28]. Carcinosarcoma of the breast and ovary have been reported in some patients with BRCA1/2 germline mutations [48,49,50].…”

Section: Serous-like Molecular Alterations In Ecsmentioning

confidence: 99%

Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma

Leskelä

Pérez-Míes

Rosa-Rosa

et al. 2019

Cancers

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Endometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At the morphological level, intratumor heterogeneity in ECS is due to an admixture of epithelial (carcinoma) and mesenchymal (sarcoma) components that can include heterologous tissues, such as skeletal muscle, cartilage, or bone. Most ECSs belong to the copy-number high serous-like molecular subtype of endometrial carcinoma, characterized by the TP53 mutation and the frequently accompanied by a large number of gene copy-number alterations, including the amplification of important oncogenes, such as CCNE1 and c-MYC. However, a proportion of cases (20%) probably represent the progression of tumors initially belonging to the copy-number low endometrioid-like molecular subtype (characterized by mutations in genes such as PTEN, PI3KCA, or ARID1A), after the acquisition of the TP53 mutations. Only a few ECS belong to the microsatellite-unstable hypermutated molecular type and the POLE-mutated, ultramutated molecular type. A common characteristic of all ECSs is the modulation of genes involved in the epithelial to mesenchymal process. Thus, the acquisition of a mesenchymal phenotype is associated with a switch from E- to N-cadherin, the up-regulation of transcriptional repressors of E-cadherin, such as Snail Family Transcriptional Repressor 1 and 2 (SNAI1 and SNAI2), Zinc Finger E-Box Binding Homeobox 1 and 2 (ZEB1 and ZEB2), and the down-regulation, among others, of members of the miR-200 family involved in the maintenance of an epithelial phenotype. Subsequent differentiation to different types of mesenchymal tissues increases tumor heterogeneity and probably modulates clinical behavior and therapy response.

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“…Due to the specific histologic feature, breast carcinosarcoma may have different biological characteristics when compared with IDC. Because of the rarity of breast carcinosarcoma, previous publications about this disease were a few small sample size retrospective analyses [ [8] , [9] , [10] , [11] , [12] , [13] , [14] ] and a few case reports [ [15] , [16] , [17] , [18] , [19] , [20] ]. From these limited studies, it appears that breast carcinosarcoma is always aggressive, poorly differentiated, and hormone receptor-negative [ 8 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Clinicopathological characteristics and survival outcomes in breast carcinosarcoma: A SEER population-based study

et al. 2020

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Objectives Carcinosarcoma of the breast is a rare disease. Its clinicopathological features and prognosis are not well defined. The aim of this study was to compare the clinicopathological features and clinical outcome between breast carcinosarcoma and breast invasive ductal carcinoma (IDC). Materials and methods Patients with breast carcinosarcoma and breast IDC were identified through the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Then a comparison was conducted between these two groups. Propensity score matching (PSM) was performed to balance the effects of baseline clinicopathological differences. The Cox proportional hazard model was used to identify potential prognostic factors of breast carcinosarcoma. Results In total, we identified 63 patients with breast carcinosarcoma and 200,596 cases with breast IDC. Comparing with IDC, breast carcinosarcoma was significantly correlated with higher grading, higher staging, larger tumor size, lower lymph node involvement, and a higher proportion of triple negative breast cancer (TNBC), suggesting a significantly worse clinical outcome. After adjusting for the uneven clinicopathological variables with PSM, significant differences were still observed between these two histology types. Subgroup analysis further showed that carcinosarcoma-TNBC has an inferior clinical outcome compared with IDC-TNBC. Finally, we identified independent prognostic factors, namely, stage, tumor size, and distant metastasis. Conclusion It is concluded that breast carcinosarcoma has distinct clinicopathological features and a significantly worse clinical outcome than common IDC.

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Carcinosarcoma of the Breast: An Aggressive Subtype of Metaplastic Cancer. Report of a Rare Case in a Young BRCA-1 Mutated Woman

Cited by 16 publications

References 22 publications

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

Molecular Features of Metaplastic Breast Carcinoma: An Infrequent Subtype of Triple Negative Breast Carcinoma

Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma

Clinicopathological characteristics and survival outcomes in breast carcinosarcoma: A SEER population-based study

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