Insulin like growth factor in breast cancer subtypes.

Abstract #3048

Background: Insulin Like Growth Factor -1 Receptor (IGF-1R) is an important new therapeutic target expressed in all cancer types. IGF-1R supports cell survival pathways implicated in resistance to cancer therapy. Knowledge of the pattern of IGF-R1 expression among breast cancer subtypes and its impact on prognosis may enhance development of therapeutics targeting this pathway.
 Methods: Patients with early breast cancer cases, stage I-III, referred to the BC Cancer Agency from 1986 to 1992 were included. Archival paraffin tissue blocks were used to construct a tissue microarray. Among 4,046 patients with early stage on the TMA, 1,238 patients (30.6 %) were excluded due to missing subtype biomarkers, IGFR staining or both. Breast cancer subtypes were defined as Luminal A (ER/PR+, HER2- and Ki67 <19%), Luminal B (ER/PR+,and HER2- and Ki67 >19%), Luminal HER2+ (HER2+ and ER/PR+), HER2 (HER2+ and ER-and PR-), and Basal {HER2-,ER-PR- and (CK 5/6+ and/or EGFR+)}. IGF-1R staining was done with Santa Cruz antibody and was scored negative if there was no or weak staining and positive if staining was moderate or strong. Chi-square and Kaplan-Meier Survival analysis were done to compare IGF-1R expression among subtypes and determine impact on Breast Cancer Specific (BCSS) and Overall Survival (OS).
 Results: A total of 2,808 evaluable cases were included with a median follow-up of 12.5 years. IGF-1R staining was scored positive in 86.4%, and negative in 13.6%. Cases with Luminal A (1,676), Luminal B (426), Luminal HER2+ (199), HER2 (206 ) and Basal (301 ) had an IGF-1R+ rate of 89.9%, 94.4 %, 83.4%, 59.2% and 76.1%, respectively (p<0.0001). 10 year BCSS was 68% (95% CI 66.0%-70.0%) in IGF-R1+ and 63% (95% CI 59.1%-66.9%) in IGF-R1 - group. Among subtypes, IGF-1R positivity was associated with improved BCSS only in Luminal A patients (p=0.015 ) and was not prognostic in other subtypes.
 Conclusion: Luminal breast cancer subtypes are associated with high rates of IGF1-R expression, while non-luminal groups have lower rates of expression. The prognostic impact of IGF-R1 expression supports the role of this pathway as a therapeutic target particularly among hormone receptor positive breast cancer.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3048.