Different effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple-negative invasive ductal breast carcinoma

Abstract

3546 Background: The insulin-like growth factor type 1 receptor (IGF-1R) is involved in progression and sensitivity to systemic treatment of breast cancer. Moreover, targeted inhibition of IGF-1R is likely to be beneficial in systemic treatment. However, it is unknown how to select patients for IGF-1R targeted therapy. Therefore, we studied the relation between IGF-1R expression and prognosis in invasive ductal breast carcinomas. Methods: Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary invasive ductal breast carcinoma. TMA sections were stained with antibodies against IGF1-R, insulin receptor (IR), ER, PR, HER-2, epidermal growth factor receptor (EGFR) and phosphorylated-Akt (p-Akt). Cytoplasmic and membranous IGF-1R staining were scored separately, as the relevance of IGF-1R cellular localization is yet unknown. Associations between IGF-1R expression with clinical and tumor characteristics were evaluated in a multivariate Cox regression model. To study in more detail the prognostic role of IGF-1R expression in triple negative invasive ductal carcinomas (TN IDCs), 51 TN IDCs from the series described above were combined with 64 TN IDCs from an independent dataset with similar patient and clinico-pathological characteristics. Results: Patients with tumors expressing both ER and cytoplasmic IGF-1R have a longer disease free survival (HR = 0.20; 95% CI 0.07 - 0.63; p-value = 0.006) and breast cancer specific survival (HR = 0.20, 95% CI 0.07 - 0.63, p-value = 0.002), independent of other known prognostic factors. Conversely, in the combined series of 105 TN IDCs, cytoplasmic IGF-1R expression was associated with a shorter disease free survival (HR = 2.29; 95% CI 1.08 - 4.48, p-value = 0.03). In a multivariate model including known prognostic factors, cytoplasmic IGF-1R expression was nearly significantly related to a shorter disease free survival (HR 2.06; 95% CI 0.95 - 4.47; p = 0.07). Conclusions: The favorable versus unfavorable association with prognosis of IGF-1R expression in ER positive versus TN IDCs may provide new opportunities to select patients for IGF-1R targeted therapy. No significant financial relationships to disclose.