A comprehensive overview of metaplastic breast cancer: clinical features and molecular aberrations

Tejaswini P Reddy, Roberto R Rosato, Xiaoxian Li, Stacy Moulder, Helen Piwnica-Worms, Jenny C Chang, Tejaswini P Reddy, Roberto R Rosato, Xiaoxian Li, Stacy Moulder, Helen Piwnica-Worms, Jenny C Chang

Abstract

Metaplastic breast cancer (MpBC) is an exceedingly rare breast cancer variant that is therapeutically challenging and aggressive. MpBC is defined by the histological presence of at least two cellular types, typically epithelial and mesenchymal components. This variant harbors a triple-negative breast cancer (TNBC) phenotype, yet has a worse prognosis and decreased survival compared to TNBC. There are currently no standardized treatment guidelines specifically for MpBC. However, prior studies have found that MpBC typically has molecular alterations in epithelial-to-mesenchymal transition, amplification of epidermal growth factor receptor, PI3K/Akt signaling, nitric oxide signaling, Wnt/β-catenin signaling, altered immune response, and cell cycle dysregulation. Some of these molecular alterations have been studied as therapeutic targets, in both the preclinical and clinical setting. This current review discusses the histological organization and cellular origins of MpBC, molecular alterations, the role of radiation therapy, and current clinical trials for MpBC.

Keywords: Epithelial-to-mesenchymal transition; Metaplastic breast cancer; NOS signaling; PI3K signaling.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
EGFR copy number variant values of mesenchymal TNBC, basal TNBC, and MpBC PDX tumors. Droplet digital PCR was performed using DNA isolated from PDX tumors, and EGFR and RPP30 (reference gene)-specific primers and probes. Red dotted line indicates the normal copy number threshold (CN 2). Pietenpol Classification [42]: BL1, basal-like 1; BL2, basal-like 2; IM, immunomodulatory; LAR, luminal androgen receptor; M, mesenchymal; MSL, mesenchymal-stem like; nd, not determined
Fig. 2
Fig. 2
MpBC harbors genetic alterations in EGFR, PIK3CA, and PTEN genes. Data derived from cBioPortal database of 9052 patients across 12 breast cancer studies
Fig. 3
Fig. 3
Overall survival curve for patients with metaplastic and non-metaplastic breast cancers. Data derived from cBioPortal database of 7548 patients across 12 breast cancer studies

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