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Androgen and Estrogen β Receptor Expression Enhances Efficacy of Antihormonal Treatments in Triple-Negative Breast

Belen Crespo1, Juan Carlos Illera1, Gema Silvan1

  • 1Department Animal Physiology, Veterinary Medicine School, Complutense University of Madrid (UCM), 28040 Madrid, Spain.

International Journal of Molecular Sciences
|February 10, 2024
PubMed

Insights

Steroid hormone inhibition shows promise for treating triple-negative breast cancer (TNBC). Androgen receptor (AR) and estrogen receptor beta (ERβ)-positive TNBC cells responded to antihormonal treatments, reducing viability and altering hormone levels.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) lacks estrogen receptor alpha (ERα), progesterone receptor (PR), and HER-2 overexpression.
  • TNBC can express androgen receptor (AR) and estrogen receptor beta (ERβ), and is influenced by steroid hormones.
  • Steroid hormone inhibition presents a potential therapeutic strategy for TNBC.

Purpose of the Study:

  • To investigate the in vitro effects of antihormonal agents dutasteride, anastrozole, and ASP9521 on human TNBC cell lines.
  • To assess the role of AR and ERβ expression in TNBC sensitivity to these treatments.
  • To analyze the impact of treatments on cell viability, proliferation, migration, and hormone levels.

Main Methods:

  • Utilized immunofluorescence, sensitivity, proliferation, and wound healing assays with human TNBC cell lines.
  • Quantified hormone concentrations to understand treatment-induced endocrine changes.
  • Correlated AR and ERβ expression levels with treatment response.

Main Results:

  • All tested TNBC cell lines expressed AR and ERβ; higher expression correlated with increased sensitivity to antihormonal therapies.
  • Dutasteride, anastrozole, and ASP9521 reduced cell viability in TNBC lines, notably MDA-MB-453 and SUM-159.
  • Treatments led to decreased androgen levels, potentially reducing cell viability, and increased estrogen levels in some lines, potentially promoting migration.

Conclusions:

  • Antihormonal treatments demonstrate potential efficacy against specific TNBC subtypes.
  • AR and ERβ expression are critical factors in determining TNBC response to steroid hormone inhibition.
  • This study highlights the significance of steroid hormone pathways in AR and ERβ-positive TNBC.
Keywords:
androgen receptorestrogen receptor betasteroid pathwaytriple-negative breast cancer

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