Abstract P4-11-22: High expression of LMTK3 is an independent factor indicating a poor prognosis in Japanese estrogen receptor α-positive breast cancer patients

Abstract

Abstract Over 70% of breast cancers are estrogen receptor α (ERα)-positive, and endocrine therapy targeting estrogen action decreases mortality from breast cancer. However, their efficacy of endocrine therapy is limited by intrinsic and acquired resistance. Recently, a novel protein kinase that regulates ERα activity, lemur tyrosine kinase-3 (LMTK3) has been identified. In this study, we investigated whether LMTK3 mRNA expression and its polymorphisms are associated with prognosis in Japanese breast cancer patients during long-term follow-up. First, we investigated the relationship between mRNA expression of LMTK3 and patient outcome in 242 breast cancers (median follow-up, 6.8 years). The effects of several variables on survival were tested by Cox proportional hazards regression analysis. Next, we performed to analyze LMTK3 rs9989661 and rs8108419 genotyping in 641 breast cancer tissues (median follow-up, 9.2 years) to clarify the prognostic role of these polymorphisms. We showed that high expression levels of LMTK3 mRNA were significantly associated with a shorter overall survival (OS) in all patients. We then, analyzed the impact of LMTK3 mRNA expression on the prognosis of breast cancer according to ERα status. Both disease-free survival and OS were significantly shorter in ERα-positive patients with high LMTK3 mRNA expression receiving adjuvant endocrine therapy than in those patients with low LMTK3 mRNA expression. Notably, the level of LMTK3 mRNA expression was not associated with prognosis in ERα-negative breast cancer patients. Univariate and multivariate Cox regression analysis of factors associated with OS revealed that high LMTK3 mRNA expression was an independent poor prognostic factor in ERα-positive breast cancer patients. Univariate and multivariate Cox regression analysis of factors associated with overall survival in ERα-positive breast cancer patientsUnivariateMultivariateVariablesn (%)P valueP valueHR (95% CI)Tumor size≤ 2cm51 (31)1 (reference)> 2cm112 (67)0.2640.2282.75 (0.57-23.5)Node statusNegative79 (47)1 (reference)Positive72 (43)0.0030.0025.25 (1.35-34.7)Grade1,2128 (77)1 (reference)327 (16)0.4850.5471.57 (0.32-6.04)LMTK3 mRNA expressionLow129 (77)1 (reference)High38 (22)0.0020.0124.94 (1.44-19.4)HR, hazard ratio; CI, confidence interval. We did not find any correlation between LMTK3 genotypes and prognosis of breast cancer patients in our series. Our results suggest that higher LMTK3 expression might be one possible mechanism for endocrine resistance in ERα-breast cancer patients, to be confirmed by further research. Citation Format: Tatsuya Toyama, Tomoko Asano, Shinya Sato, Nobuyasu Yoshimoto, Yumi Endo, Yukari Hato, Dong Yu, Satoru Takahashi, Yoshitaka Fujii. High expression of LMTK3 is an independent factor indicating a poor prognosis in Japanese estrogen receptor α-positive breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-11-22.