Abstract P4-07-01: Profiling miRNA in high risk post-operative early breast cancer patients to detect possible association to correlation with immune system antitumor response
Authors: Tzschaschel MLJ , Rack B , Majunke L , Trapp EK , Mahner S , Fasching PA , Fehm T , Schneeweiss A , Friedl TWP , Polasik A , Janni W , Alunni-Fabbroni M 
Published: March 2017

Aims: Identifying which patient will be the one who developes metastatis or relapses is still an unsolved problem in breast cancer research. Circulating free nuclei acids such as microRNA (miRNA) are very promising cancer biomarkers to detect those patients. Aim of this study was to unravel an association among whole blood miRNA profiling, circulating tumor cells (CTCs) and clinical outcome in early breast cancer (EBC) patients and to test the utility of miRNAs as prognostic and diagnostic markers in post-operative patients.

Methods: 48 high risk EBC patients, a subsample of the German SUCCESS A trial, were included in this retrospective study together with 18 aged-matched healthy donors (HDs) as controls. Peripheral blood was drawn post-operatively before (T0), after (T1) and two years after (T2) chemotherapy directly in Tempus Blood RNA Tubes (ThermoFischer Scientific) to stabilize and isolate total RNA. miRNAs were quantified by qPCR and their relative expression was calculated according to the 2-DCt method. CTCs were detected by immunocytochemistry. Data were analyzed using non-parametric statistical tests and p-values below 0.05 were considered significant.

Results: 8 different miRNAs, either with oncogenic (miR-10a, -19a, -21, -22) or tumor suppressive (miR-20a, -127, -155, -200b) properties, in most of the cases linked to immune system regulation (miR-19a, -20a, -21, -127 and -155) were tested. miR-19a, miR-21, miR-22 and miR-127 showed the most promising results as prognostic markers in our tests. They could differentiate patients from HDs (Patients vs. HD: miR-19a at T0, p=0.004), T1 ( p&lt;0.0001), miR-21 at T0 (p=0.001), T1 (p=0.004), miR-22 at T1 (p=0.012), T2 (p=0.034)). Additionally they correlated with the post-operative detection of CTCs (miR-127) and the late development of metastasis (miR-19a). Kaplan-Meier analysis indicated a borderline association between a longer progression free survival and higher miR-19a levels (HR= 2.808, 95% confidence interval [CI] =0.904, p=0.074.)

Conclusion: We found a panel of miRNAs that could discriminate post-operative patients from HDs and could predict patients' outcome. We suggest that whole blood miRNA profiling could unravel a correlation with the activation of the immune system, leading to an efficient antitumor response and a better clinical outcome. These findings could open new perspectives in immune oncology and personalized therapy already in the early phase of the disease.

Citation Format: Tzschaschel MLJ, Rack B, Majunke L, Trapp EK, Mahner S, Fasching PA, Fehm T, Schneeweiss A, Friedl TWP, Polasik A, Janni W, Alunni-Fabbroni M. Profiling miRNA in high risk post-operative early breast cancer patients to detect possible association to correlation with immune system antitumor response [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-07-01.