Abstract P6-03-11: Differences in serum miRNA signatures in women with pathology-confirmed breast cancer, benign breast diseases and healthy individuals with no cancer history
Authors: Akiyama H , Manlapaz V , Wong C , Yamazaki Y , Knapp M , Ohara S 
Published: February 2018

[INTRODUCTION] Mammography is the principal non-invasive imaging method of screening for breast cancer around the world. Mammography has been shown to be effective in reducing breast cancer deaths in randomized studies (Tabar et al., 2011 and Duffy et al., 2002). However, screening mammography can result in false positives that require subsequent interventions such as biopsy or interval repeat mammography.

Recently, circulating micro RNAs (miRNAs) have been cited as promising minimally invasive markers for breast cancer as well as for various other types of malignancies (Shimomura et al., 2016; Lawrie et al., 2008; Wang et al., 2009; Zhang et al., 2010; Mitchell et al., 2008). In this study, we have developed a new molecular diagnostic platform for the measurement of circulating (serum) miRNAs to assist with the management of women with abnormal screening mammograms.

[METHODS] Peripheral venous blood samples were collected in BD Red/Gray gel barrier tubes from patients with untreated breast cancer, patients with benign breast diseases and healthy individuals with no cancer history. The processing from blood to serum was done within six hours of collection and stored at -80°C. Total RNA was extracted from 300uL of the resulting serum using 3D-Gene®RNA extraction reagent (Toray Industries, Inc). Comprehensive miRNA expression analysis was then performed using 3D-Gene® Human miRNA Oligo Chip (Toray Industries, Inc). The average of three pre-selected internal control miRNA (miR-149-3p, miR-2861 and miR-4463) was used to normalize the signals across the different microarrays tested.

[RESULTS] RESULTS] All serum specimens used in this study were from subjects enrolled at US clinical sites (83% Caucasian, 15% African American, 2% Asian and others). One hundred fifteen (115) specimens (breast cancer: 40, healthy: 45, benign breast lesions: 30) were selected as a training cohort and used to develop comprehensive discriminants with 1–5 miRNAs using Fisher's linear discriminant analysis. The analysis identified a combination of five miRNAs that could detect breast cancer, and the resulting discriminant equation showed a sensitivity of 90.5%, specificity of 89.5% and accuracy of 89.8%. As test cohorts, (A) 381 subjects (breast cancer: 63, healthy: 160, benign breast lesions: 152), independent from subjects in the training cohort, and (B) 35 subjects who had been referred for breast biopsy were tested. The discrimination performance of the equation for each breast cancer stage (Stage 0: 1, Stage 1: 20, Stage 2: 17, Stage 3: 14, Stage 4: 11) was examined in the test cohorts. Also, information from breast cancer types as well as from benign breast lesions have been used to assess the performance of the discriminant score. The results of these analyses along with a discussion of the potential significance and plans for expanded clinical trials will be presented.

Citation Format: Akiyama H, Manlapaz V, Wong C, Yamazaki Y, Knapp M, Ohara S. Differences in serum miRNA signatures in women with pathology-confirmed breast cancer, benign breast diseases and healthy individuals with no cancer history [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 P6-03-11.