Oestrogen receptor co-activator AIB1 is a marker of tamoxifen benefit in postmenopausal breast cancer

Abstract

BackgroundThe oestrogen receptor (ER) co-activator amplified in breast cancer 1 (AIB1) has been suggested as a treatment predictive and prognostic marker in breast cancer. Studies have however not been unanimous.Patients and methodsAIB1 protein expression was analysed by immunohistochemistry on tissue micro-arrays with tumour samples from 910 postmenopausal women randomised to tamoxifen treatment or no adjuvant treatment. Associations between AIB1 expression, clinical outcome in the two arms and other clinicopathological variables were examined.ResultsIn patients with ER-positive breast cancer expressing low tumour levels of AIB1 (<75%), we found no significant difference in recurrence-free survival (RFS) or breast cancer-specific survival (BCS) between tamoxifen treated and untreated patients. In patients with high AIB1 expression (>75%), there was a significant decrease in recurrence rate (HR 0.40, 95% CI 0.26–0.61, P < 0.001) and breast cancer mortality rate (HR 0.38, 95% CI 0.21–0.69, P = 0.0015) with tamoxifen treatment. In the untreated arm, we found high expression of AIB1 to be significantly associated with lower RFS (HR 1.74, 95% CI 1.20–2.53, P = 0.0038).ConclusionOur results suggest that high AIB1 is a predictive marker of good response to tamoxifen treatment in postmenopausal women and a prognostic marker of decreased RFS in systemically untreated patients.

Reprogramming of the ERRα and ERα Target Gene Landscape Triggers Tamoxifen Resistance in Breast Cancer

“…The cumulating evidence, which argues against a strong contribution (40,41), is consistent with our data as we detected a downregulation of AIB1 in recurrent tamoxifen-resistant tumors.…”

Activator of thyroid and retinoid receptor increases sorafenib resistance in hepatocellular carcinoma by facilitating the Warburg effect

“…Activator of thyroid and retinoid receptor (known as SRC‐3), located in a frequently amplified region, 20q12, is overexpressed in multiple cancers, such as breast, liver, gastric and prostate cancer 14,25‐27 . However, the detailed mechanisms and influence of ACTR on carcinoma treatment still require investigation.…”

Salinomycin overcomes acquired tamoxifen resistance through AIB1 and inhibits cancer cell invasion in endocrine resistant breast cancer

“…AIB1 is a nuclear receptor co‐activator and works as a prognostic marker that promotes breast cancer growth and tamoxifen resistance . AIB1 amplification and over‐expression were found in aggressive breast cancers associated with high histological grade, poor prognosis and tamoxifen resistance . Our findings suggested that salinomycin was able to increase tamoxifen sensitivity by decreasing mRNA and protein expression of AIB1 in endocrine‐resistant breast cancer cells.…”