P4-01-19: SRC-1 Expression Is a Prognostic Factor of Breast Cancer-Specific and Disease-Free Survival in Inflammatory Breast Cancer.

Le résumé fourni par la source

Abstract Background: Steroid receptor coactivator (SRC-1 to 3) proteins drive nuclear receptor transcriptional activity by modulating transcriptional processes such as chromatin modification, transcription initiation, chain elongation, and RNA splicing. In patients who display resistance to endocrine treatment, SRC-1 has been implicated in the conversion of tamoxifen anti-agonist activity to its agonist profile. SRC-1 expression is a prognostic of DFS in breast cancer, but its role in inflammatory breast cancer (IBC) remains unknown. Materials and Methods: SRC-1 protein levels were measured by immunohistochemistry in 103 IBC and 11 normal, non-cancer related samples, diagnosed at the Centre Pierre & Marie Curie (Algiers, Algeria). Staining results were correlated with protein levels of ER, PR, and HER2, and clinico-pathological variables, breast cancer-specific (BCSS) and disease-free survival (DFS), and response to tamoxifen treatment. Results: SRC-1 was positive in all normal breast tissue, as well as in 66% of IBC samples. SRC-1 positivity was associated with worse OS (P<0.001) and DFS (P=0.004). SRC-1 expression correlated with worse BCSS (P=0.011), and marginally with DFS (P=0.046) in tamoxifen-treated patients, but strongly with DFS (P=0.007) in patients who received no endocrine therapy as indicated by Kaplan-Meier and log-Rank analyses. Multivariate analysis showed that SRC-1 (Hazard Ratios (HR): 5.2; 95%CI: 2.0−13.6; P<0.001) and Her2 (HR: 3.1; 95%CI: 1.2−8.1; P=0.02) expression were independent prognostic markers of BCSS. SRC-1 (HR: 4.8; 95%CI: 1.9−12.2; P<0.001), Her2 (HR: 2.4; 95%CI: 1.0−5.7; P=0.05), and hormone treatment (HR: 0.4; 95%CI: 0.2−0.8; P=0.01) were independent prognostic markers of DFS. Discussion: Determining prognosis and predicting response to endocrine treatment is of paramount importance in the search for personalized treatment. SRC-1 expression predicts worse OS, DFS, and, similar to non-IBC, predicts DFS independently of endocrine therapy. This study highlights the importance of SRC-1 expression as a strong prognosticator of BCSS and disease recurrence in IBC patients. *Supported by an UICC ICRET Fellowship (ICR/09/043 to Dr. Chaher) and by New Mexico State IBC funding (New Mexico Senate Bill 532). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-01-19.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.