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

Abstract

<jats:p>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.</jats:p>

Case Report of a Breast Mass with Three Types of Malignant Tumors—Squamous Cell Carcinoma, Invasive Ductal Carcinoma, and Breast Sarcoma

“…The squamous cell carcinoma and invasive ductal carcinoma were treated similarly as triple negative breast cancer. 10 Chemotherapy based on anthracycline and paclitaxel has been reported to effectively control the disease. 11 A gene model can be proposed to assess patient prognosis.…”

Construction and Validation of a Prognostic Model for the Assessment of Postoperative Overall Survival of Patients with Metaplastic Breast Cancer: Based on a Retrospective Large Data Analysis and Chinese Multicenter Study

“…Although the expression mechanism is not yet clear, this provides a theoretical basis for the treatment of MBC using the immune system [31] . Many mutated genes have been detected in MBC, and the most frequency mutated genes, TP53 and PIK3CA, suggest a direction for investigating targeted therapy [31][32][33].…”

An Update on the Molecular Pathology of Metaplastic Breast Cancer

“… 21 Mutation frequencies reported for MpBC range from 26%-75% for TP53 , and 23%-70% for PIK3CA ( Table 1 ) and this is supported by a recent meta-analysis of 14 studies encompassing 539 cases. 22 Other than TP53 and PIK3CA , the most frequently identified mutations across multiple cohorts occur in PTEN, NF1, HRAS, PIK3R1 . Emerging data support that the various morphologic elements feature subtly different mutation profiles, with for example, a lack of PIK3CA mutations found in those MpBC with chondroid differentiation.…”