Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast

Semir Vranic, Juan Palazzo, Souzan Sanati, Elena Florento, Elma Contreras, Joanne Xiu, Jeffrey Swensen, Zoran Gatalica

Research output: Contribution to journalArticle

10 Scopus citations


Introduction: Neuroendocrine carcinoma (NEC) of the breast is a rare, special type of breast cancer, reportedly constituting 2% to 5% of all breast cancers. Although breast NEC does not have a specific targeted therapy, several new targeted therapies based on specific biomarkers were recently investigated in the NEC of lung and in other types of breast carcinoma, which may provide guidance to their feasibility in breast NEC. Materials and Methods: Twenty breast NECs were profiled for biomarkers of therapy including antibody-drug conjugates (DLL3, TROP-2, and FOLR1), histone deacetylase (H3K36Me3) inhibitors, tropomyosin receptor kinases (NTRK1/2/3 gene fusions) targeted inhibitors, alkylating agents (MGMT), and immune checkpoint inhibitors (PD-L1, TMB, and MSI) using immunohistochemistry and DNA/RNA next-generation sequencing assays. Results: Predictive expression of TROP-2, FOLR1, and H3K36Me3 were detected in different subsets of tumors and may pave the way for development of novel targeted therapies in some patients with breast NECs. There was no evidence of DLL3 expression, NTRK gene fusions, or MGMT hypermethylation. No biomarkers predictive of immune checkpoint inhibitor efficacy (programmed death-ligand 1 expression, tumor mutational burden, microsatellite instability) were identified. FGFR and CCND1 gene amplifications were detected in isolated cases. Conclusions: This study identified several potential targets for novel therapies in breast NEC, including farletuzumab and mirvetuximab soravtansine (FOLR1), sacituzumab govitecan (TROP-2), and HDAC inhibitors (H3K36Me3). In some cases, CCND1 gene amplification may indicate the usefulness of investigational therapies. The reported results should serve as an early indication of potential clinical relevance in selected patients with breast NEC.

Original languageEnglish
Pages (from-to)131-136
Number of pages6
JournalClinical breast cancer
Issue number2
StatePublished - Apr 2019


  • Biomarkers
  • Breast cancer
  • Molecular profiling
  • Special types
  • Targeted therapy

Fingerprint Dive into the research topics of 'Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast'. Together they form a unique fingerprint.

  • Cite this

    Vranic, S., Palazzo, J., Sanati, S., Florento, E., Contreras, E., Xiu, J., Swensen, J., & Gatalica, Z. (2019). Potential Novel Therapy Targets in Neuroendocrine Carcinomas of the Breast. Clinical breast cancer, 19(2), 131-136. https://doi.org/10.1016/j.clbc.2018.09.001