Abstract P2-05-05: Canine invasive mammary carcinoma as a spontaneous model for insulin-like growth factor-1 receptor-overexpressing triple negative breast cancer

Abstract

Abstract Background: Dogs spontaneously develop invasive mammary carcinoma with a high prevalence of the triple-negative subtype, making this model relevant for the investigation of new therapeutic pathways. Insulin-like growth factor-1 receptor (IGF-1R) is extensively involved in malignant transformation, proliferation and metastasis in human breast cancer and multiple clinical trials have used IGF-1R inhibitors with encouraging results. Aims: To quantify IGF-1R expression in canine triple-negative invasive mammary carcinoma (TN-CMC) and assess its prognostic value (overall, specific and disease-free survival). To validate the dog as a spontaneous animal model for preclinical trials targeting IGF-1R in triple-negative breast cancer. Material and methods: 104 triple-negative canine invasive mammary carcinomas (Estrogen receptor negative, Progesterone receptor negative, not HER2 overexpressing) were included. Bitches were followed for at least 2 years after mastectomy. TN-CMC were classified as basal-like (Cytokeratin-CK 5/6 positive and/or Epidermal Growth Factor Receptor-EGFR positive) and non-basal-like (CK 5/6 and EGFR negative). IGF-1R expression (clone G11) was quantified using the same scoring system as for HER2 in breast cancer. Results: 68.3% (n = 71/104) of the TN-CMC were classified as basal-like and 31.7% (n = 33/104) as non-basal-like. 45.2% (n = 47/104) of TN-CMC overexpressed IGF-1R (score 3+), of which 70.2% (n = 33/47) were basal-like and 61.7% (n = 29/47) were grade III. Univariate and multivariate analyses revealed that IGF-1R overexpression (score 3+) was associated with significantly shorter overall, specific and disease-free survivals (median: 163, 332 and 278 days respectively) than weak (score 1+) IGF-1R expression (median: 842 days, not achieved and 1011 days respectively). Conclusion and perspectives: IGF-1R overexpression is common and related to a poor outcome in canine triple-negative invasive mammary carcinoma. Preclinical studies using the dog as a spontaneous animal model for triple-negative breast cancer could be considered to investigate new therapies targeting IGF-1R. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-05-05.