Extending aromatase inhibitor sensitivity in hormone resistant breast cancer

Angela M.H. Brodie, Gauri J. Sabnis, Saranya Chumsri, Angela M.H. Brodie, Saranya Chumsri, Sara Sukumar, Angela M.H. Brodie

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Aromatase inhibitors (AIs) are first-line treatment for ER + breast cancer. However, despite responses initially, some patients can eventually acquire resistance. Moreover, 25% of all breast cancer patients do not express the estrogen receptor (ERα) and are innately resistance. In tumors of mouse models with acquired AI letrozole resistance, expression of ERα was reduced whereas HER2/growth factor signaling was enhanced. Treatment of mice with trastuzumab (HER2 antibody) reduced HER2/p-MAPK but restored ERα expression. The addition of trastuzumab to letrozole treatment when tumors progressed resulted in significantly longer tumor suppression than these drugs alone. Thus, inhibition of both HER2 and ERα signaling pathways was necessary to overcome resistance. In ERα-negative tumors, the receptor has been shown to be silenced by epigenetic modifications. Treatment of MDA-MB-231 ER-negative tumors with a histone deacetylase inhibitor, entinostat (ENT) increased expression of ERα and also aromatase. When ENT was combined with letrozole, tumor growth rate was markedly reduced compared with control tumors. ENT plus letrozole treatment also prevented the colonization and growth of MDA-MB-231 cells in the lung with significant reduction in visible and microscopic foci. These novel strategies could improve treatment for patients with acquired and innate resistance to AIs.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalHormone Molecular Biology and Clinical Investigation
Volume5
Issue number2
DOIs
StatePublished - 2011

Keywords

  • aromatase inhibitors
  • breast cancer
  • letrozole
  • trastuzumab

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Molecular Biology
  • Endocrinology

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  • Cite this

    Brodie, A. M. H., Sabnis, G. J., Chumsri, S., Brodie, A. M. H., Chumsri, S., Sukumar, S., & Brodie, A. M. H. (2011). Extending aromatase inhibitor sensitivity in hormone resistant breast cancer. Hormone Molecular Biology and Clinical Investigation, 5(2), 97-103. https://doi.org/10.1515/HMBCI.2011.010