US EPA

6314286 

Journal Article 

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

Smollich, M; Götte, M; Fischgräbe, J; Radke, I; Kiesel, L; Wülfing, P 

2009 

Yes 

Anticancer Research
ISSN: 0250-7005
EISSN: 1791-7530 

29 

6 

2167-2171 

English 

19528477 

WOS:000267389500038 

BACKGROUND: Estrogen receptors (ER) alpha and beta 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 ERalpha/ERbeta 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 ERbeta (relative quantification [RQ]=0.83, p=0.019), while transition from grade 1 to grade 3 tumors was associated with the decrease of ERalpha expression (RQ=1.14 vs. RQ=0.65, p<0.001). In stimulation assays, tamoxifen and fulvestrant increased ERalpha expression to RQ=1.51 (p=0.01) and RQ=1.42 (p<0.001), respectively, and left ERbeta unchanged. In contrast, aromatase inhibitors up-regulated ERbeta 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 ERalpha expression, while aromatase inhibitors increase ERbeta expression, which may contribute to the aromatase inhibitors' therapeutic superiority over antiestrogens. 

Breast cancer; ER alpha; ER beta; SERM; aromatase inhibitor