A high AR:ERα or PDEF:ERα ratio predicts a sub-optimal response to tamoxifen therapy in ERα-positive breast cancer
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Approximately 30% oestrogen receptor alpha (ERα)-positive breast cancer (BC) patients exhibit intrinsic or recurrent resistance to adjuvant endocrine therapy with tamoxifen. The androgen receptor (AR) is expressed in about 90% of ERα-positive patients, with particularly high expression in tamoxifen-resistant tumours. Prostate-derived Ets factor (PDEF), which is a co-regulator of AR, plays a role in tamoxifen resistance in ERα-positive BC. The purpose of this research was to analyse the potential roles of AR, PDEF and ERα levels in the response to tamoxifen resistance in ERα-positive BC.
The nuclear AR:ERα and PDEF:ERα ratios were examined immunohistochemically in a cohort of 225 ERα-positive pre-menopausal BC patients who had received adjuvant tamoxifen therapy.
For both AR:ERα and PDEF:ERα ratios, the optimal cutoff value was 2.0. Patients receiving adjuvant tamoxifen treatment who had a high AR:ERα (≥ 2.0) (HR = 3.90) or PDEF:ERα ratio (≥ 2.0) (HR = 2.77) had a beyond twofold increased risk of failure. Both the AR:ERα ratio (P = 0.001) and PDEF:ERα ratio (P = 0.002) were independently associated with the risk of tamoxifen treatment failure. Furthermore, both a high ratio of AR:ERα (≥ 2.0) and PDEF:ERα (≥ 2.0) were associated with shorter disease-free survival (DFS) and shorter disease-specific survival (DSS). In addition, both the AR:ERα ratio and PDEF:ERα ratio were independent predictors of DFS (both P < 0.0001) and DSS (P = 0.001 and P < 0.0001, respectively).
AR:ERα and PDEF:ERα ratios are independent predictors of the response to conventional ERα-directed tamoxifen endocrine therapy.
KeywordsProstate-derived Ets factor Androgen receptor Oestrogen receptor alpha Tamoxifen Breast cancer
We thank the BC patients and their families. They generously donated valuable tissue samples.
This study was funded by National Natural Science Foundation of China (Grant Numbers 81172532, 81602340).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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