To get more insight into the role of AR in breast cancer, we additionally performed a retrospective pooled analysis to determine the prognostic value of the AR using mRNA profiles of 7270 primary breast tumors.
Recent advances in the molecular classification of breast tumours have uncovered a subset of breast tumours associated with high expression of androgen receptor mRNA including the so-called 'luminal androgen receptor (LAR) tumours' and 'molecular apocrine tumours' (MATs).
It has also been documented that AR is expressed in more than 60% of breast tumors, which promotes the growth of estrogen receptor-negative (ER<sup>-</sup>)/AR-positive (AR<sup>+</sup>) breast cancer cells.
In addition, C1orf64 closely correlated with AR expression in primary and metastatic breast tumors and C1orf64 expression was relatively higher in breast tumors with a lower grade and lobular histology.
Re-evaluation of the breast tumor immunohistochemistry has shown positive androgen receptor expression and negative expression for estrogen, progesterone and HER-2 receptors.
A majority (~70%) of breast tumors are found to express estrogen receptor, and a significant portion (~90%) of ER-positive (ER<sup>+</sup>) breast tumors are also androgen receptor-positive (AR<sup>+</sup>).
Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria.
These findings are in agreement with the hypothesis that AR may stimulate or inhibit breast cancer growth depending on ER status, AR transactivation, and the endocrine-metabolic environment of breast tumors.
Furthermore, gene encoding coagulation factor VII (F7) demonstrated the closest expression pattern with AR (CC=0.716) in the dataset and factor VII protein expression was significantly associated to that of AR in a cohort of 209 breast tumors.
In AR negative breast tumours, mutation screening identified the same mutation (T105A) in the 5'UTR of two AR negative breast cancer patients but not reported in the normal human population.
Significant differences in AR levels existed among different breast tumor subtypes (highest in estrogen receptor-positive and/or progesterone receptor-positive tumors) as well as by PIK3CA mutation status (P < 0.0001 for both).
In order to define AR in breast cancer, 67 primary breast tumours and 8 normal breast samples as control tissue were analysed for AR expression at the mRNA and protein levels using RT-PCR and Western blotting, respectively.
Here we have developed and validated a real-time RT-PCR assay to quantify AR gene expression at the mRNA level in a series of 131 patients with unilateral invasive primary breast tumors.