Abstract 4574: FGFR1 amplification in high grade, estrogene receptor positive and metastasized breast cancers

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL Background: The FGFR1-gene (fibroblast growth factor receptor 1) is located at chromosome 8p12 encoding for a tyrosine kinase. FGFR1 is involved in cell cycle, differentiation, survival, apoptosis, and angiogenesis. Recently, it was shown that breast cancer cell lines harboring a FGFR1 amplification were more sensitive to treatment with an FGFR inhibitor. To estimate if FGFR inhibitors can be a therapeutic option in human breast cancer we investigated the prevalence and the histological subtypes of FGFR1 amplification in a large cohort of breast cancers. Methods: Tissue micro-arrays with 907 breast cancers were hybridized using the commercially available fluorescent in-situ hybridization probe (FGFR1/CEN8; ZytoVision®). The results were interpreted as following: a normal gene status was considered as a ratio (FGFR1/CEN8): 0.8-1.9, an amplification was defined as a ratio β2.0, a polysomy was defined as more than >4 FGFR1 and CEP8 signals. Results: FGFR1 amplification was observed in 8.9% (n=81), a normal gene status was found in 80.7% (n=732), and a polysomy was detected in 10.2% (n=93) tumors. FGFR1 amplified breast cancers showed the following features: expression of estrogen receptor 85% (67/78), ductal 72.8% (59/81), high grade (G3) 45.5% (35/77), her2 over-expression (score2+/3+) 16% (12/75), and 18% (13/72) recurrence. Comparing T (T1, T2, T3) and N (N0 and >N0)-categories between FGFR1 amplified and non-amplified tumors the following results were seen: T1: 25% (19/77) vs. 34% (245/719), T2: 56% (43/77) vs. 48% (345/719), T3: 9% (7/77) vs. 6% (43/719), N0: 44.5% (28/63) vs 53% (338/641), >N0: 55.5% (35/63) vs 47% (303/641). We could observe a slight better long term overall survival in patients treated with anti-hormonal therapy and FGFR1 amplified breast cancers (p=0.085). Conclusions: FGFR1 amplification is prevalent (8.9%) in breast cancer, especially among the most frequent subtypes such as estrogen receptor positive breast cancers (10%) and ductal type (8%). Further, FGFR1 amplified breast cancer showed often unfavorable/aggressive features such as a high tumor grade (45.5%), larger tumor diameter, and metastasis (55.5%). These patients are a clinically relevant group since they need aggressive adjuvant treatment regimen. The detection of FGFR1 amplification could help in the identification of some patients already at higher risk which might benefit from a new therapeutic option with FGFR1 inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4574. doi:1538-7445.AM2012-4574