Abstract P3-08-11: The prognostic impact of retinoic acid-induced 2 (RAI2) expression in ERα-positive breast cancer patients

Abstract

Abstract Background: Breast cancer cells disseminate to the bone marrow and form bone metastases in a large majority of late-stage patients. Retinoic Acid-Induced 2 (RAI2) was reported as a putative suppressor of early hematogenous dissemination of tumor cells to the bone marrow in breast cancer, particularly in estrogen receptor α (ERα)-positive breast cancer. Here, we investigated mRNA expression of RAI-2 in breast cancer patients during long-term follow-up. Materials and methods: A total of 451 invasive breast cancer tissues was available for analysis of RAI2 mRNA using a TaqMan PCR system. We also sought correlations between clinicopathological factors and levels of RAI2 expression in these samples. The expression of markers associated with tumor-initiating capacity, such as SNAI1, SNAI2 and VIM was also analyzed. The median follow-up period was 9.0 years. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values. Results: We found positive correlations between low expression of RAI2 mRNA and shorter disease-free survival and overall survival in breast cancer patients (P=0.003, P<0.0001, respectively), which was limited to ERα-positive patients (P=0.04, P=0.0009, respectively), and not seen in ERα-negative patients (P=0.52, P=0.27, respectively). Low RAI2 mRNA levels were positively correlated with high grade, ERα-negativity and PgR negativity. Multivariate analysis indicated that low level RAI2 mRNA expression was an independent factor for survival both overall in breast cancer and in ERα-positive breast cancer patients Multivariate analysis (ERα-positive breast cancer patients) OS Multivariate patientsp valueHR(95%CI)Tumor size≤2cm1390.83691 (Reference) >2cm207 1.08(0.54-2.28)Node statusNegative176<0.00011 (Reference) Positive144 4.72(2.33-10.34)Grade11240.95921 (Reference) 2•3218 0.98(0.50-2.14)RAI2 mRNA expressionhigh140<0.00011 (Reference) middle•low206 4.79(2.14-12.78) . Conclusion:We show that low expression of RAI2 is an independent factor predictive of a poor prognosis in ERα-positive breast cancer patients. RAI2 could be a promising candidate biomarker and therapeutic target in ERα-positive breast cancer to prevent dissemination to the bone marrow. Citation Format: Nishikawa S, Kondo N, Endo Y, Hato Y, Hisada T, Nishimoto M, Dong Y, Okuda K, Kato H, Takahashi S, Nakanishi R, Toyama T. The prognostic impact of retinoic acid-induced 2 (RAI2) expression in ERα-positive breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-11.