Ano1/TMEM16A Overexpression Is Associated with Good Prognosis in PR-Positive or HER2-Negative Breast Cancer Patients following Tamoxifen Treatment.

Abstract

The calcium-activated chloride channel Ano1 (TMEM16A) is overexpressed in many tumors. Although Ano1 overexpression is found in breast cancer due to 11q13 amplification, it remains unclear whether signaling pathways are involved in Ano1 overexpression during breast cancer tumorigenesis in vivo. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) have been known to contribute to breast cancer progression. It is unclear whether Ano1 is associated with clinical outcomes in breast cancer patients with different ER, PR and HER2 status. In the present study, we investigated the Ano1 expression in 431 patients with invasive ductal breast carcinoma and 46 patients with fibroadenoma, using immunohistochemistry, and analyzed the association between Ano1 expression and clinical characteristics and outcomes of breast cancer patients with different ER, PR, and HER2 status. Ano1 was overexpressed in breast cancer compared with fibroadenoma. Ano1 was significantly more associated with breast cancer with the lower clinical stage (stage I or II), or triple-negative status. Mostly importantly, Ano1 overexpression was associated with good prognosis in patients with the PR-positive or HER2-negative status, and in patients following tamoxifen treatment. Multivariate Cox regression analysis showed that Ano1 overexpression was a prognostic factor for longer overall survival in PR-positive or HER2-negative patients, and a predictive factor for longer overall survival in patients following tamoxifen treatment. Our findings suggest that Ano1 may be a potential marker for good prognosis in PR-positive or HER2-negative patients following tamoxifen treatment. The PR and HER2 status defines a subtype of breast cancer in which Ano1 overexpression is associated with good prognosis following tamoxifen treatment.