Low Androgen Receptor Expression Is Associated with Distant Metastases in Patients with Androgen Receptor Expressing Triple-Negative Breast Carcinoma
Lisa Sutton, Kwame E Torgbe, Dengfeng Cao, Venetia Sarode, Kyle Molberg, Barbara Haley, Yan Peng. UT Southwestern, Dallas, TX; Washington University School of Medicine, St Louis, MO
Background: High androgen receptor (AR) expression in breast cancer has been correlated with a decreased risk of recurrence and death, and significant differences in AR expression have been identified in different subtypes of breast cancer. Triple-negative (TN) breast carcinoma, characterized by negativity of estrogen receptor, progesterone receptor, and Her2, is a group of aggressive tumors that characteristically have a low AR expression. Further characterization of AR expression in TN tumors may help elucidate prognosis and treatment options.
Design: 91 patients were identified with TN breast tumors, 87 of which were basal-like with positivity of CK5/6 and/or EGFR. Of these patients, 32 had distant metastatic disease (pM1) and 59 had local disease only (pM0). Immunohistochemical staining for AR, Ki67 and p53 was performed. The frequency and percent of intratumoral expression of AR was compared between the pM1 and pM0 groups to explore an association of AR expression with metastatic disease in TN tumors. Also, AR expression levels were correlated with Ki67 expression, p53 expression and tumor size.
Results: The frequency of AR positivity was similar between the two groups with 34.38% positive pM1 cases and 35.59% positive pM0 cases. Among AR positive cases, intratumoral expression was significantly higher in the pM0 group (57.24% ±7.74) compared to the pM1 group (29.18% ±11.69; p=0.04). The expression of AR also showed a significant negative correlation with Ki67 expression (r=-0.51, p<0.001). No correlation was found with p53 expression or tumor size.
Conclusions: Our results reveal that among AR positive TN breast tumors, distant metastases (pM1) are significantly associated with a lower intratumoral expression of AR as compared to cases with only local disease (pM0). The results suggest TN tumors with a higher expression of AR may be less likely to develop metastatic disease. High Ki67 expression has been previously associated with a worse prognosis in TN tumors. The significant negative correlation of AR expression with Ki67 provides further support that high AR levels may be associated with a better prognosis in TN tumors, which might be related to the antiproliferative effect of AR stimulation. AR expression levels may have potential prognostic value in AR expressing TN tumors. Targeting the AR pathway may be a novel therapeutic approach for the treatment of TN tumors.
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 27, Wednesday Afternoon