Mini-gene profiling for the prediction of bone metastases in breast cancer patients.

Abstract

e21030 Background: The process of bone metastasization includes numerous steps such as proliferation, invasion and adhesion, involving molecules, growth factors, chemochines and their receptors that confer the bone-like phenotype. Thus, only cancer cells with specific features will be able to reach and colonize bone tissue. The early prediction of relapse in this site could be clinically useful to select patients for a tailored therapy based on bone specific drugs such as bisphosphonates or RANK-L inhibitors. Methods: The study retrospectively evaluated the levels of TFF1, DKK1, IBSP, HPSE, SPP1, Agr2, SPARC, CTGF, COMP, FST, and RANK transcripts by quantitative real-time PCR in the fresh frozen breast cancer samples of 40 patients to predict cancer relapse and the sites of relapse. Fifteen patients had no evidence of disease (NEDP), 15 had bone metastases (BMP), and 10 had visceral metastases (VMP). The predictive accuracy of each marker was calculated using Receiver Operating Characteristic (ROC) curves. Results: The median values of each marker were calculated for each subgroup: TFF1 median values were about 7 times higher in BMP than in control groups (p=0.05); COMP and HPSE median values were about twice as high in BMP compared to both NEDP and VMP. The area under the curve (AUC) was 0.73 for TFF1, and 0.62 for HPSE and COMP. Considering markers as dichotomous variables, TFF1 expression reached 67% in BMP compared to 21% and 20 % in NEDP and VMP, respectively. TFF1 was also analyzed in combination with other markers and, considering positivity of at least one marker among TFF1, DKK1, and IBSP, an expression level of 80% was reached for the BMP group, whilst the same low expression level was maintained in both control groups (p=0.041). Conclusions: Our preliminary results show that the analysis of 3 gene expression markers, TFF1, DKK1 and IBSP, in primary breast tumors could be useful to predict the patients who will relapse to bone tissue. However, a larger case series should be performed to understand the role of these markers in the selection of patients eligible for adjuvant preventive bone specific therapy.