Abstract
Background and objective: The androgen receptor (AR) is a member of the steroid receptor subfamily with well-known biological and therapeutic importance in prostate cancer. There is evidence that the androgen signalling pathway may play a critical role also in normal and malignant breast tissue. They are highly expressed in triple negative breast cancer (TNBC) but it is not clear if AR expression is correlated with survival in advanced TNBC. Therefore, in the present study we investigated the prognostic value of AR expression in metastatic TNBC. Patients and methods: Stage IV TNBC was included in the analysis. Patients with poor performance status (ECOG>2) were excluded. Tumors with >10% nuclear-stained cells were considered to be positive for AR. Univariate and multivariate analyses were performed. Results: From a database of 208 TNBC patients, 24 cases of advanced TNBC were identified; out of 24 patients, 33% were AR positive. The median age at diagnosis was 61 years (range 30-78 years). All patients included in the study received first-line chemotherapy for their disease. Median progression free-survival (mPFS) and overall survival (OS) were 3.5 months (range 0.3-27.3 months) and 25.9 months (range 2.52-122.2 months), respectively. Univariate analysis showed that AR negative advanced TNBC had a significantly worse PFS (3.2 vs 7.9 months; p=0.02; HR=2.57, 95% CI 1.15-10.53) and OS (20.5 vs 47.4 months; p=0.01; HR=2.88, 95% CI 1.32- 9.43). Multivariate analysis confirms that AR expression was an independent prognostic factor of PFS (p=0.04; HR=2.19, 95% CI 1.52-5.91), as well as for OS (p=0.05; HR=2.21, 95% CI 0.98-2.55). Conclusions: Our preliminary results suggested that the assessment of AR expression may be a useful tool to identify patients with a good or a poor prognosis. Furthermore, since that about one third of metastatic TNBC expressed ARs, they may represent a target for novel potential treatment options in advanced TNBC.
Highlights
Triple negative breast cancers (TNBC), characterized by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and an absence of human epidermal growth factor receptor-2 (HER-2) overexpression, are a clinical problem because they often present with higher rates of visceral metastases, a relatively shorter median survival of 7-13 months and have a limited duration of response to chemotherapy [1,2,3,4,5,6]
Univariate analysis showed that androgen receptor (AR) negative advanced triple negative breast cancer (TNBC) had a significantly worse Progression-free survival (PFS) (3.2 vs 7.9 months; p=0.02; HR=2.57, 95% confidence intervals (CIs) 1.15-10.53) and overall survival (OS) (20.5 vs 47.4 months; p=0.01; HR=2.88, 95% CI 1.329.43)
Multivariate analysis confirms that AR expression was an independent prognostic factor of PFS (p=0.04; HR=2.19, 95% CI 1.52-5.91), as well as for OS (p=0.05; HR=2.21, 95% CI 0.98-2.55)
Summary
Triple negative breast cancers (TNBC), characterized by lack of expression (or minimal expression) of estrogen receptor (ER), progesterone receptor (PR) and an absence of human epidermal growth factor receptor-2 (HER-2) overexpression, are a clinical problem because they often present with higher rates of visceral metastases, a relatively shorter median survival of 7-13 months and have a limited duration of response to chemotherapy [1,2,3,4,5,6]. Most of women progress quickly on systemic therapy and have a poor survival, but some may have a slower progressive course It may reflect an underlying biological diversity of TNBC, probably due to the activation of intracellular pathways that are related with tumor survival and proliferation. The androgen signalling pathway may play a critical role in normal and malignant breast tissue [13]. There is evidence that the androgen signalling pathway may play a critical role in normal and malignant breast tissue. They are highly expressed in triple negative breast cancer (TNBC) but it is not clear if AR expression is correlated with survival in advanced TNBC. In the present study we investigated the prognostic value of AR expression in metastatic TNBC
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