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).
Lack of expression of androgen receptor may play a critical role in transformation from in situ to invasive basal subtype of high-grade ductal carcinoma of the breast.
Association of repeat polymorphisms in the estrogen receptors alpha, beta (ESR1, ESR2) and androgen receptor (AR) genes with the occurrence of breast cancer.