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Old 05-23-2014, 11:48 AM   #5
'lizbeth
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Re: Tamoxifen Mechanism

AIB1 expression predicted response to tamoxifen treatment in postmenopausal women

Weiner M. Ann Oncol. 2013;doi:10/1093/annonc/mdt159.



  • August 5, 2013
High levels of the estrogen receptor co-activator amplified in breast cancer 1 appeared to predict response to tamoxifen treatment among postmenopausal women with breast cancer.
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Researchers also reported an association between amplified in breast cancer 1 (AIB1) expression and shortened RFS among women who did not undergo adjuvant treatment.
Prior studies have demonstrated between AIB1 and breast cancer survival, but the results have not been consistent.
In the current study, researchers randomly assigned 910 postmenopausal women to receive tamoxifen treatment or no adjuvant treatment.
The researchers used immunohistochemistry on tissue micro-arrays to analyze AIB1 protein expression.
Among patients with ER-positive breast cancer that expressed low tumor levels of AIB1, defined as less than 75%, researchers reported no significant difference in breast cancer-specific survival or RFS between those treated with tamoxifen and those who were assigned to the no-treatment arm.
Among patients with high AIB1 expression, defined as higher than 75%, researchers reported a significant decrease in breast cancer mortality (HR=0.38; 95% CI, 0.21-0.69) and recurrence (HR=0.40; 95% CI, 0.26-0.61) among those who underwent tamoxifen treatment. When adjusting for tumor size, progesterone receptor and HER-2 positivity, researchers found significant interaction between AIB1 and tamoxifen (P=.023).
Among untreated patients, high expression of AIB1 was significantly associated with shorter RFS (HR=1.74; 95% CI, 1.20-2.53), according to researchers.
“AIB1 has been shown to enhance the effects of estrogen, which may be in accordance with the view of AIB1 as a negative prognostic factor that at the same time predicts good benefit from tamoxifen,” the researchers wrote. “However, this study does not exclude that a minor subgroup of patients with ER-positive tumors simultaneously overexpressing AIB1 and HER-2 exhibit resistance to tamoxifen.”
Disclosure: The researchers report funding from the Swedish Cancer Society and the Swedish Research Council.
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