Abstract
BackgroundThe androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes. Despite the high frequency of AR expression in breast cancer its appraisal remains controversial because its role is complex, dependent on the hormonal milieu. The aim of the current study was to investigate the frequency of AR and ER positive CETCs in breast cancer patients.MethodsThe number of vital CETCs was determined from blood of 66 patients suffering from breast cancer and the expression of AR and ER on these cells was investigated using the maintrac method.ResultsNumbers of CETCs/mL blood were significantly higher in patients with advanced disease as compared to patients with early stage disease. The fraction of AR positive CETCs was significantly higher than the fraction of ER positive CETCs (90% vs. 50%; P < 0.001). Patients with positive lymph nodes had less AR positive CETCs as compared to patients with negative lymph node status. The AR:ER ratio was higher in patients receiving tamoxifen therapy as compared to patients without tamoxifen therapy whereas treatment with aromatase inhibitor had no influence on AR:ER ratio.ConclusionsThe ratio of AR to ER positive CETCs, obviously, is influenced by endocrine therapy, more specifically therapy with tamoxifen. Since AR expression seems to be one of the possible mechanism of resistance to endocrine therapy this may provide a new biomarker to select patients who might benefit from combination treatment of ER and AR inhibitors.
Highlights
The androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes
The receiver operating characteristic (ROC) curve shows that the number of Circulating epithelial tumor cells (CETCs) was a predictor of advanced stage of disease
The percentage of AR positive CETCs was significantly higher in triple negative breast cancers (TNBC) as compared to hormone receptor positive patients (Fig. 4b)
Summary
The androgen receptor (AR) is expressed in the majority of breast cancers and across the main breast cancer subtypes. A high AR:ER protein ratio has been reported to be indicative of a shorter time to relapse in patients treated with tamoxifen [6] Despite these emerging data, the role of AR in breast cancer is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood [1]. Circulating tumor cells are rare tumor cells that escape from solid tumors, travel into peripheral blood and can seed distant metastases They have been reported to be a surrogate marker for tumor treatment response in primary breast cancer [10], and their presence has been linked to shorter survival in patients with metastatic breast, prostate, colorectal and lung cancer [1]. The purpose of our study was to better characterize AR and ER expression on CETCs in breast cancer contributing a new biomarker for targeted AR therapy, especially in patients with tamoxifen resistance
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