Androgen Receptor Expression
Androgen Receptor Expression
We sought to determine the prevalence of androgen receptor (AR) expression in a predominantly estrogen receptor (ER)-negative subset of breast cancers and delineate the immunohistochemical and clinical associations, including whether AR expression has prognostic significance in ER-negative tumors. We identified 69 ER-negative and 19 ER-positive breast cancer cases with concurrent immunohistochemical prognostic panels (ER, PR, HER-2/neu, Ki-67, and p53); immunohistochemical analysis was performed for AR using standard techniques. Clinical data were extracted from medical records. χ tests were used to assess associations between variables. AR was found in 49% (34/69) of ER-negative and 89% (17/19) of ER-positive cases. In ER-negative tumors, AR was associated with increased age (P = .02), postmenopausal status (P < .001), tumor grade (P = .03), tumor size (P = .03), and HER-2/neu overexpression (P = .003). In ER-positive tumors, AR was associated with progesterone receptor expression (P < .03). In univariate analysis of ER-negative tumors, patients with AR-positive tumors had significantly better disease-free survival (P = .049). AR is expressed in a significant number of ER-negative cases and shows significant associations with important clinical and pathologic prognostic factors.
The role of hormone receptors as prognostic and therapeutic tools has widespread acceptance in the management of breast cancer. The expression of estrogen receptor (ER), in particular, is thought to be of great importance, predicting an approximately 50% to 75% response rate to hormonal therapy, while ER-negative tumors have a less than 10% chance of response. ER positivity also is prognostic of delayed recurrence in primary breast cancer. The data concerning progesterone receptor (PR) are not as clear, but ER-negative tumors with PR are thought to have an intermediate response rate compared with ER- and PR-positive tumors. In addition, estrogen is thought to play a major role in the development and progression of breast cancer.
Androgens also are thought to have an important role in breast cancer. The risk of breast cancer is increased in postmenopausal women with high estrogen levels as well as in women with high androgen levels. The mechanism by which androgens contribute to breast cancer is not well understood, but studies have shown that androgens can induce proliferative changes in breast tissue, and animal models have shown that administration of both estrogen and androgens can induce tumor formation. Also, recent studies have shown that the breast cancer susceptibility gene 1 (BRCA1) is a coactivator of the androgen receptor (AR).
Studies of AR expression in breast cancer have shown that AR is expressed in the majority of ER-positive tumors; however, these studies have not emphasized the expression of AR in ER-negative tumors; most had a majority of ER-positive tumors. In addition, while some of these studies found that expression of AR predicted response to hormonal therapy and overall survival, they also showed that AR status was not predictive of disease-free survival in patients with ER-positive tumors. In these studies, ER status, not AR status, was an independent prognostic factor for disease-free survival.
The purposes of the present study were to analyze expression of AR in paraffin-fixed tissues in a subset of patients from a university hospital with predominantly ER-negative tumors and to correlate AR expression with other prognostic variables as well as clinicopathologic data, including disease-free survival.
We sought to determine the prevalence of androgen receptor (AR) expression in a predominantly estrogen receptor (ER)-negative subset of breast cancers and delineate the immunohistochemical and clinical associations, including whether AR expression has prognostic significance in ER-negative tumors. We identified 69 ER-negative and 19 ER-positive breast cancer cases with concurrent immunohistochemical prognostic panels (ER, PR, HER-2/neu, Ki-67, and p53); immunohistochemical analysis was performed for AR using standard techniques. Clinical data were extracted from medical records. χ tests were used to assess associations between variables. AR was found in 49% (34/69) of ER-negative and 89% (17/19) of ER-positive cases. In ER-negative tumors, AR was associated with increased age (P = .02), postmenopausal status (P < .001), tumor grade (P = .03), tumor size (P = .03), and HER-2/neu overexpression (P = .003). In ER-positive tumors, AR was associated with progesterone receptor expression (P < .03). In univariate analysis of ER-negative tumors, patients with AR-positive tumors had significantly better disease-free survival (P = .049). AR is expressed in a significant number of ER-negative cases and shows significant associations with important clinical and pathologic prognostic factors.
The role of hormone receptors as prognostic and therapeutic tools has widespread acceptance in the management of breast cancer. The expression of estrogen receptor (ER), in particular, is thought to be of great importance, predicting an approximately 50% to 75% response rate to hormonal therapy, while ER-negative tumors have a less than 10% chance of response. ER positivity also is prognostic of delayed recurrence in primary breast cancer. The data concerning progesterone receptor (PR) are not as clear, but ER-negative tumors with PR are thought to have an intermediate response rate compared with ER- and PR-positive tumors. In addition, estrogen is thought to play a major role in the development and progression of breast cancer.
Androgens also are thought to have an important role in breast cancer. The risk of breast cancer is increased in postmenopausal women with high estrogen levels as well as in women with high androgen levels. The mechanism by which androgens contribute to breast cancer is not well understood, but studies have shown that androgens can induce proliferative changes in breast tissue, and animal models have shown that administration of both estrogen and androgens can induce tumor formation. Also, recent studies have shown that the breast cancer susceptibility gene 1 (BRCA1) is a coactivator of the androgen receptor (AR).
Studies of AR expression in breast cancer have shown that AR is expressed in the majority of ER-positive tumors; however, these studies have not emphasized the expression of AR in ER-negative tumors; most had a majority of ER-positive tumors. In addition, while some of these studies found that expression of AR predicted response to hormonal therapy and overall survival, they also showed that AR status was not predictive of disease-free survival in patients with ER-positive tumors. In these studies, ER status, not AR status, was an independent prognostic factor for disease-free survival.
The purposes of the present study were to analyze expression of AR in paraffin-fixed tissues in a subset of patients from a university hospital with predominantly ER-negative tumors and to correlate AR expression with other prognostic variables as well as clinicopathologic data, including disease-free survival.
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