Metaplastic Breast Cancer (MBC)

Overview

Metaplastic Breast Cancer (MBC) is a rare and aggressive subtype of invasive breast cancer characterized by differentiation of neoplastic cells toward non-glandular lineages (squamous, spindle, chondroid, or osseous elements). It sits at OncoTree level 2 under the BREAST parent node. MBC is predominantly ER-negative/PR-negative and often triple-negative, with poor response to conventional chemotherapy. The metaplastic phenotype is closely linked to epithelial-to-mesenchymal transition (EMT) and lineage plasticity.

Cohorts in the corpus

  • MBC is referenced as the mouse-model counterpart in cross-species breast cancer modeling studies; mouse mammary tumors generated by intraductal AAV-CRISPR editing of Tp53, Pik3caH1047R, or KrasG12D uniformly produced ER-/PR- metaplastic tumors with squamous differentiation — in contrast to ER+/PR+ ductal carcinomas produced by identical edits in rats PMID:26437033.

Recurrent alterations

  • In mouse mammary models, KrasG12D, PIK3CA-H1047R, and PIK3CA-H1047R+TP53 Indel editing consistently produced ER-/PR- metaplastic tumors with squamous differentiation, while the same edits in rats yielded ER+ ductal carcinoma — illustrating species-dependent lineage plasticity and suggesting that the metaplastic phenotype is not driven exclusively by specific oncogene combinations but by species/cell-of-origin context PMID:26437033.
  • Lenti-HrasQ61L intraductal delivery also produced ER-/PR- metaplastic tumors in mice but ER+/PR+ ductal carcinoma in rats, reinforcing the context-dependency of metaplastic transdifferentiation PMID:26437033.

Subtypes

  • Mouse MBC models produced in the AAV-CRISPR platform display widespread squamous differentiation regardless of the driving oncogene (Kras, Pik3ca, Hras), distinguishing them from ER+ rat ductal carcinomas generated by identical genetic edits PMID:26437033.

Therapeutic landscape

  • The metaplastic/ER- phenotype in mouse models precludes endocrine therapy; these tumors did not respond to fulvestrant or ovariectomy, in contrast to the endocrine-sensitive ER+ rat tumors — highlighting MBC’s lack of hormone-receptor dependence PMID:26437033.

Sources

  • PMID:26437033 — Bu et al., Rat somatic genome editing enables ER+ breast cancer modeling, bioRxiv 2025.

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