Differential effects of aromatase inhibitors and antiestrogens on estrogen receptor expression in breast cancer cells

Martin Smollich, Martin Götte, Jeanett Fischgräbe, Isabel Radke, Ludwig Kiesel, Pia Wülfing*

*Corresponding author for this work
11 Citations (Scopus)

Abstract

Background: Estrogen receptors (ER) α and β play an important role in breast cancer. Recently, systemic adjuvant endocrine therapy with selective estrogen receptor modulator (SERM) tamoxifen has been challenged by aromatase inhibitors. Compared to antiestrogens, third-generation aromatase inhibitors (anastrozole and letrozole) exhibit an improved efficacy and tolerability. Materials and Methods: Using real-time PCR analysis, 21 breast cancer tissue samples were analysed for a change of the ERα/ERβ ratio during malignant progression. In stimulation experiments, differential effects of SERMs, ER antagonists and aromatase inhibitors have been investigated. Results: Transition from normal breast to grade 1 tumors was characterized by down-regulation of ERβ (relative quantification [RQ]=0.83, p=0.019), while transition from grade 1 to grade 3 tumors was associated with the decrease of ERα expression (RQ=1.14 vs. RQ=0.65, p<0.001). In stimulation assays, tamoxifen and fulvestrant increased ERα expression to RQ=1.51 (p=0.01) and RQ=1.42 (p<0.001), respectively, and left ERβ unchanged. In contrast, aromatase inhibitors up-regulated ERβ to RQ=1.23 (anastrozole, p=0.029) and RQ=1.38 (letrozole, p=0.048). Conclusion: Taken together, data indicate that SERMs/antiestrogens and aromatase inhibitors exhibit opposed effects on the ER expression of breast cancer cells: tamoxifen and fulvestrant up-regulate ERα expression, while aromatase inhibitors increase ERβ expression, which may contribute to the aromatase inhibitors' therapeutic superiority over antiestrogens.

Original languageEnglish
JournalAnticancer Research
Volume29
Issue number6
Pages (from-to)2167-2171
Number of pages5
ISSN0250-7005
Publication statusPublished - 06.2009

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

Fingerprint

Dive into the research topics of 'Differential effects of aromatase inhibitors and antiestrogens on estrogen receptor expression in breast cancer cells'. Together they form a unique fingerprint.

Cite this