Abstract 85: Prognostic stratification of naturally occurring canine triple negative invasive mammary carcinoma according to IGF1-R and AR expression
Authors: Jaillardon Laetitia , Loussouarn Delphine , Abadie Jérome , Siliart Brigitte , Campone Mario , Nguyen Frédérique 
Published: May 2015

Abstract
Triple negative breast cancer (TNBC) lacking ER-Estrogen Receptor and PR-Progesterone Receptor expression and HER2-Human Epidermal Growth Factor Receptor 2 overexpression, is a highly aggressive and heterogeneous disease for which better understanding and targeted treatments are needed. Insulin-like growth factor-1 receptor (IGF-1R) and androgen receptor (AR) are frequently expressed in TNBC and correlate with prognosis, making them potential candidates for new therapeutic pathways. Dogs spontaneously develop invasive mammary carcinoma with a high prevalence of the triple negative subtype (TNCMC). We therefore aimed to quantify AR and IGF-1R expression in naturally occurring TNCMC and assess their combined prognostic value in terms of overall (OS), specific (SS) and disease-free survivals (DFS). 104 TNCMC were included (ER&lt;10%, PR&lt;10%, HER2&lt;3+ by IHC-immunohistochemistry). Female dogs were followed for at least 2 years after mastectomy. 71 TNCMC were basal-like (CK5/6-Cytokeratin and/or EGFR-Epidermal Growth Factor Receptor positive) and 33 non basal-like (CK5/6 and EGFR negative). IGF-1R expression (clone G11) was quantified using the same scoring system as for HER2 in breast cancer. AR expression (clone SP107) was considered positive if there were at least 1% positive tumor nuclei. 47/104 (45%) TNCMC overexpressed IGF-1R (3+ IHC score). 40/104 (38%) TNCMC were AR positive. IGF-1R overexpression positively correlated with lymphovascular invasion (LVI) (p=0.01). AR expression negatively correlated with LVI (p&lt;0.01).
IGF-1R and AR IHC expression stratified TNCMC into 3 groups with different outcomes: AR positivity defined the TN Luminal-AR group (n=40); among AR-negative cases, IGF-1R scores 2+ and 3+ defined the TN IGF-1R+ group (n=54); other cases were defined as “all negative”: TN All-Neg group (n=10).
By univariate analysis, OS significantly differed (p=0.02) among groups with hazard ratio (HR) of 0.8 (95% CI 0.3-1.6) for the TN All-Neg group and 1.7 (1.1-2.6) for the TN IGF1R+ group compared to the TN Luminal-AR group. SS was also significantly different (p&lt;0.01) with respective HR of 0.6 (0.2-1.9) in the AllNeg group and 2.3 (1.3-4.0) in the IGF-1R+ group. DFS, defined as the interval from mastectomy to the first local recurrence or lymph node metastasis, was shorter in the TN IGF-1R+ group (HR=2.3; 95% CI 1.2-4.1; p=0.02) than in the TN Luminal-AR group.
By multivariate analysis, the stratification of TNCMC according to AR and IGF-1R expression was an independent prognostic factor associated with DFS and SS with grade, LVI and completeness of excision as covariates.
IGF-1R overexpression and AR positivity are common in canine triple-negative invasive mammary carcinoma. Our result revealed the value of using a combination of IGF-1R and AR for the prognostic stratification of TNCMC with a potential translational application to human triple negative breast cancer.
Citation Format: Laetitia Jaillardon, Delphine Loussouarn, Jérome Abadie, Brigitte Siliart, Mario Campone, Frédérique Nguyen. Prognostic stratification of naturally occurring canine triple negative invasive mammary carcinoma according to IGF1-R and AR expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 85. doi:10.1158/1538-7445.AM2014-85