Expression of androgen receptor in inflammatory breast cancer may have therapeutic significance

Inflammatory breast cancer (IBC) is a rare and very aggressive disease with characteristic symptoms that include redness, swelling, tenderness, and warmth in the breast because of dermal lymphatic occlusion by tumor emboli. Despite multimodality treatment approaches, the prognosis of patients with IBC remains poor, with a clinical outcome much worse than that of patients with non-inflammatory breast cancer. Identifying novel therapeutic targets is highly desirable.

Emerging evidence is indicating that the androgen-signaling pathway plays a role in breast carcinogenesis through regulating estrogen-responsive genes. Androgen receptor (AR) expression in breast cancer has become an interesting topic of research, because AR can be targeted by anti-androgen agents such as bicalutamide and enzalutamide, which have been widely used to treat patients with AR-positive, advanced prostate cancers. Similar to estrogen receptor (ER) and progesterone receptor (PR), AR is a member of the steroid hormone receptor family. Depending on the study population, testing method, and cutoff values used, AR reportedly is expressed in 70% to 90% of invasive breast cancers.

A significant association between AR and ER expression has been reported in breast carcinoma, not otherwise specified (NOS).Peters et al observed coexpression of the 2 receptors in 80% to 90% of breast tumor cells.AR positivity also reportedly is associated with older age and/or postmenopausal status at diagnosis, smaller tumor size, lower tumor grade, negative human epidermal growth factor receptor 2 (HER2) status, and negative lymph node metastasis. However, AR positivity is also reported in 30% to 50% of ER-negative/PR-negative and triple-negative tumors.

To date, the prevalence of AR expression in IBC tumors and its association with survival in patients with IBC have not been evaluated. The objectives of the current study were to examine the prevalence of AR expression in IBC tumors and to explore its prognostic value. Yun Gong published a study included 88 patients with primary IBC who were treated at The University of Texas MD Anderson Cancer Center from September 1994 to August 2004 and for whom tumor tissue and clinical follow-up information were available. The diagnosis, preoperative and postoperative treatments of these patients, biomarker study (encompassing ER, PR, and HER2 status), and tissue microarray (TMA) construction have been previously reported.Notably, ER, PR, and HER2 status and tumor characteristics were evaluated on pretreated tumor samples obtained by core-needle biopsy, and a TMA was built up using postneoadjuvant residual tumors. This study was approved by the Institutional Review Board.

In this study, the median follow-up was 10.8 years (range, 0.7-14.5 years), and the 5-year OS and DSS rate were 46% and 49%, respectively. AR was positive in 39% of IBC tumors overall, and in 33.3% of ER-negative tumors, 29.3% of PR-negative tumors, and 42.6% of triple-negative tumors. Positive AR expression was significantly associated with lymphovascular invasion (P = .01). However, there was no significant association between AR positivity and ER, PR, or HER2 status or other pathologic parameters , but there was a trend toward an association between AR and PR expression (P = .07)

无标题

The study demonstrated that AR is commonly expressed in post-treated IBC tumors. AR positivity was significantly associated with lymphovascular invasion, and there was a trend toward an association between AR expression and PR expression. Patients who had IBC with AR-negative/ER-negative tumors had significantly worse OS and DSS than patients who had tumors that exhibited other combinations of AR/ER status. For patients with AR-positive IBC tumors, an AR-modulated therapeutic approach may add to the existing treatment to improve patients’ outcomes. Further study with a larger series will be required to delineate the biologic mechanisms of AR and their clinical significance in IBC tumors.

Reference:

Expression of androgen receptor in inflammatory breast cancer and its clinical relevance. Cancer.2014;120:1775-1779

Leave a Reply

Your email address will not be published. Required fields are marked *

*

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>