Breast cancer: Role of IGF-1 and IGFBP-3 expression in prognostication

Deregulation of Insulin like growth factors (IGF) is an important determinant of breast carcinogenesis. Circulatory IGF-1 (potent breast mitogen) and IGFBP-3 (its regulator) are extensively evaluated; few studies report transcript copy numbers (CN) from ex-vivo samples. This study from 106 patients evaluated mRNA expression (qRT-PCR CN) of IGF-1 and IGFBP-3 for prognostic and predictive utility from tumor, adjacent normal tissues (ANT) and lymph nodes. The differences in IGF-1 and IGFBP-3 mRNA levels (CN/mu g RNA) were juxtaposed to clinical and pathologic variables and survival. Tumors expressed lower IGF-1 and higher IGFBP-3 as compared to ANT. Both transcript levels decreased with increasing age. Primary tumors with nodal involvement, Invasive Lobular carcinoma (ILC) histology and stromal involvement showed increased transcript levels than their respective counterparts. Moreover, surviving patients showing no relapse had higher expression of both molecules. Early stage and necrosed tumors expressed higher IGFBP-3 while a trend of lower expression was seen as tumor grade advanced. IGF-1 expression was inversely correlated to stage, histologic grade and. Significantly different Relapse Free Survival (RFS) was seen with IGFBP-3 up-/down-regulation considering progesterone receptor (PR) status but not estrogen receptor (ER) and HER-2 while the Overall Survival (OS) was similar for both these molecules. We conclude that expression of these molecules may aid prognostication and success of anti IGF-1 strategies.