Androgen receptor and metastasis-associated protein-1 are frequently expressed in estrogen receptor negative/HER2 positive breast cancer

Abstract

The prognostic value of androgen receptor (AR) and its related molecules in breast cancer is not well characterized. We retrospectively investigated 120 ER⁺ and 120 ER⁻ invasive breast cancers of 240 women, who were treated at our institution between January 2008 and December 2009. We excluded in situ, recurrent, metastatic, and bilateral carcinomas as well as non-epithelial lesions. Median follow-up was 74 months. Immunohistochemical assessment of expression of AR and metastasis-associated protein-1 (MTA1) resulted in 59.2 % (n = 142) AR⁺ and 36.7 % (n = 88) high MTA1 expressing (MTA1^High) carcinomas. MTA1^High tumors were significantly more often ER⁻, while AR⁺ tumors were significantly more often HER2⁺ (p < 0.01). MTA1^High/ER⁻ tumors were more often AR⁻/HER2⁻ (p < 0.01). Patients with an AR⁺/ER⁺ tumor had better disease-free survival (DFS; p = 0.011). Patients with an ER⁻/MTA1^High tumor had significantly shorter DFS (p = 0.006) as well as patients with an AR⁺/HER2⁺ tumor (p < 0.01). In Cox models, AR expression (HR, 0.248; 95 % CI, 0.086–0.716) and lymph node status (HR, 6.401; 95 % CI, 1.428–28.686) were independent predictors for DFS in ER⁺ cancers, whereas AR⁺/HER2⁺ expression status (HR, 2.927; 95 % CI, 1.256–6.821) and lymph node status (HR, 2.690; 95 % CI, 1.041–7.840) were independent predictors for DFS in ER⁻ cancers. We show that AR might be an additional marker for endocrine responsiveness in ER⁺ cancers and suggests that blocking MTA1 might be an effective way to inhibit AR/HER2 signaling in ER⁻ breast cancer.

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