Abstract
Abstract Background: Chemotherapy plays a major role in its treatment, though overtreatment is frequent since its choice is based on clinicopathological prognostic data. The identification and validation of new predictive profiles or markers continues to be relevant. New findings may contribute to achieve better results in this area, as well as to provide new targets of the pathways involved in chemoresistance. Karyopherin α2 (KPNA2), low density lipoprotein receptor-related protein 8 (LRP8) and growth and differentiation factor 15 (GDF15), are three candidate predictive biomarkers in breast cancer, previously identified on DNA microarrays reports. Methods: Using tissue microarrays technology and immunohistochemistry, we compared the expression of these three markers between cases of breast cancer with response to chemotherapy (absence of recurrence), and those with failure (with recurrence). All patients received chemotherapy based on anthracyclines and taxanes. Potential confounding factors, as known recurrence and progression risk factors, were controlled for during the comparison. Results: 20 out of 63 patients had tumor recurrence. Potential confounding factors were similar among cases with response and failure to chemotherapy. For KPNA2 no differences were found between cases with response or failure. LRP8 showed higher expression in cases with failure to chemotherapy (mean 7.22 vs 14.01%, p =0.025). In Cox multivariable regression analysis, which included potential confounding factors as covariates, only LRP8 remained as a significant predictive factor (HR 1.28, p=0.016). GDF15 showed no expression in our cases, nor in an external set of cases. Conclusions: We demonstrated increased expression of LRP8 in breast cancer cases recurring after chemotherapy. KPNA2 and GDF 15 showed no predictive value for chemotherapy response in our study. LRP8 is a potential predictive marker worth of further investigation for its role in chemoresistance as well as for its potential validation. Note: This abstract was not presented at the meeting. Citation Format: Hector Maldonado-Mtz, Alonso-Luna Oscar, Ali Flores-Perez, Meneses-Garcia Abelardo, Erika B. Ruiz-Garcia, Cesar Lopez-Camarillo, Horacio Astudillo-de la Vega. Predictive value of LRP8, KPNA2 and GDF15 expression to anthracycline/taxane based chemotherapy response in patients with locally advanced breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1786. doi:10.1158/1538-7445.AM2017-1786
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