However, most breast tumors are eventually resistant to tamoxifen therapy.
Extensive researches were conducted to understand the molecular mechanisms involved in tamoxifen resistance, and have revealed that multiple signaling molecules and pathways such as EGFR and HER2 are involved in tamoxifen resistance.
Currently, the mechanisms by which tamoxifen sensitive breast cancer cells acquire these signaling pathways and develop tamoxifen resistance have not been elucidated.
The identification of ER-α36, a variant of ER-α, that is able to mediate agonist activity of tamoxifen provided great insights into the underlying mechanisms of tamoxifen resistance.
Resistant cell lines were generated over a prolonged period of time using the MCF-7aro (aromatase overexpressed) breast cancer line.
These cell lines are resistant to the aromatase inhibitors letrozole, anastrozole and exemestane and the anti-estrogen tamoxifen, for comparison.
Indeed, on a molecular level, 70-75% of invasive breast cancers are oestrogen receptor positive (ER ) and proliferate in response to oestrogen,  as Beatson deduced.
However, this important drug has its limitations: its efficacy is frequently hampered by the phenomenon of tamoxifen resistance.
This article provides an overview of ER breast cancer biology relevant to understanding the complexities of tamoxifen resistance.
Two types of resistant cell lines have been generated, those that grow in the presence of testosterone (T) which is needed for cell growth, and resistant lines that are cultured in the presence of inhibitor only (no T).
In addition to functional characterization of aromatase and ERα in these resistant cell lines, microarray analysis has been employed in order to determine differential gene expression within the aromatase inhibitor resistant cell lines versus tamoxifen, in order to better understand the mechanism responsible for AI resistance on a genome-wide scale.