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Breast Cancer Research News

Borley AC , et al. Anti-oestrogens but not oestrogen deprivation promote cellular invasion in intercellular adhesion-deficient breast cancer cells. Breast Cancer Res. 2008 Dec 4;10(6):R103. [Epub ahead of print]

Borley and colleagues investigated the effects of tamoxifen and fulvestrant treatment on invasive signalling and compared this with the direct effects of oestrogen deprivation using endocrine-sensitive MCF-7 cells, in the presence or absence of functional E-cadherin. The authors studied the effect of oestrogen and 4-hydroxy-tamoxifen on the invasive capacity (as determined by Matrigel invasion assays) of these cells. Western blotting using phospho-specific antibodies was performed to ascertain changes in invasive signalling in response to the two anti-oestrogens versus oestradiol treatment and withdrawal. The authors observed that tamoxifen was able to promote an invasive phenotype in ER-positive breast cancer cells in the absence of functional E-cadherin. This suggests a role for Src kinase and associated pro-invasive genes in this process. The study showed that although this adverse effect was also apparent for the steroidal anti-oestrogen fulvestrant, it was absent during oestrogen withdrawal. These findings are also consistent with a recent study showing that the absence of E-cadherin predicts tamoxifen resistance in patients with ER+ve breast cancer. Therefore it may be prudent to consider the use of aromatase inhibitors in preference to anti-oestrogens in patients with ER+ve and E-cadherin-ve breast cancer.