Abstract 1212: Anaplastic lymphoma kinase (ALK) gene copy number gain in inflammatory breast cancer (IBC): frequency, clinicopathologic features and prognostic implication .

Abstract

Abstract BACKGROUD The aim of this study is to evaluate prevalence of ALK and MET copy number change and its relation to clinicopathologic characteristics and prognosis of patients with IBC. METHODS This study included 32 patients diagnosed as IBC between August 2000 and December 2011 from three cancer centers in Republic of Korea. ALK gene copy number change and rearrangement were assessed using FISH technique and ALK expression was assessed by IHC assay from biopsy or surgical pathology of IBC patients. FISH analysis of MET was also performed in same patient group. We determined disomy as ALK CNG (-); trisomy (3 fusion signals in ≥30% of cells) and polysomy (≥4 fusion signals in ≥ 10% of cells) as ALK CNG (+). Clinicopathologic characteristics, expression status of ER, PR, HER-2, progression-free survival (PFS) and overall survival (OS) were compared according to ALK gene copy number status. RESULTS The median PFS and the median OS of IBC patients were 22.5 months and 37.2 months, and 50% and 34.4% of patients were HER-2 positive and triple negative breast cancer (TNBC), respectively. ALK CNG was observed in 17 patients (53%) out of 32 IBC patients and none had EML4-ALK rearrangement. IHC assay of ALK revealed moderate to strong cytoplasmic staining in majority of tumor cells in all IBC patients, but H-score was not correlated to ALK copy number status (p=0.417). The clinical characteristics of the patients were similar between ALK CNG (-) and ALK CNG (+) group, and proportion of TNBC is higher in ALK CNG (+) patients, but without statistical significance. (47.1% in ALK CNG (+) vs 20.0% in ALK CNG (-), p=0.147) All brain metastasis during follow up period occurred only in ALK CNG (+) patients. (4 patients) At a median follow-up of 17.6 months (range, 1.6-47.0), ALK CNG (+) patients showed worse PFS than patients with ALK CNG (-) patients (median PFS; 12.7months vs 34.3 months), but without statistical significance. (p = 0.274) Overall survival was worse in ALK CNG (+) patients compared to ALK CNG (-) patients (median OS; 24.9 months vs 60.6 months) with marginal statistical significance. (p= 0.074) Multivariate analysis of OS with adjustment for factors including cancer stage, mastectomy, HER2 positivity also revealed worse OS of ALK CNG (+) patients with marginal significance. (HR, 3.60; 95% CI, 0.962-13.463; p = 0.057). Increased MET copy number observed in 42.9% of IBC patients, but it was not related to PFS and OS of IBC patients (p=0.402, p=0.249), and there was no correlation between ALK and MET copy number change. CONCLUSION This study showed significant frequency of ALK CNG in IBC patients. ALK CNG was associated to poor overall survival in IBC patients in this study. Our finding suggests that ALK CNG may have a prognostic significance in IBC patients and their biological significance and relation to susceptibility to ALK inhibitor need to be elucidated. Citation Format: Min Hwan Kim, Joo Hyuk Sohn, Ja Seung Koo, In Hae Park, Kyung Hae Jung, Soohyeon Lee. Anaplastic lymphoma kinase (ALK) gene copy number gain in inflammatory breast cancer (IBC): frequency, clinicopathologic features and prognostic implication . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1212. doi:10.1158/1538-7445.AM2013-1212