Abstract 3995: Breast cancer molecular subtypes are reflected in circulating microRNA profiles
Authors: Huo Dezheng , Clayton Wendy M. , Yoshimatsu Toshio F. , Chen Jianjun , Olopade Olufunmilayo I. 
Published: August 2015

Abstract
Background: Breast cancer is a heterogeneous disease. Triple-negative breast cancer (TNBC) as defined by negativity in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), has a distinct disease course and response to treatment, compared with ER+ breast cancer. Circulating microRNAs (miRNAs) have been suggested as promising diagnostic and early detection biomarkers for cancer, including breast cancer, as miRNAs can be detected in extra-cellular biofluids at stable levels. However, findings from previous studies of circulating miRNA are inconsistent, which may be in part due to the heterogeneity nature of breast cancer.
Methods: To characterize the differential expression pattern of circulating miRNAs in TNBC from ER+ breast cancer, we performed a whole miRNome profiling experiment using Exiqon miRCURY microRNA qRT-PCR Human panels which include 752 miRNAs. Total RNA was extracted from 200ul serum of 27 luminal A-like breast cancer patients (ER+/PR+/HER2-), 18 TNBC, and 31 volunteer controls who did not have breast cancer. After global mean normalization, we used linear models and empirical Bayes methods to examine expression differences across the three groups. Benjamini and Hochberg's false discovery rate method was used to correct for multiple testing. Penalized logistic regression was used to build a profile of miRNAs that can distinguish TNBC from luminal A-like breast cancer.
Results: The mean age was similar between the three groups (luminal A-like: 51.1, TNBC: 52.5, and controls: 50.6 years old). A total of 226 miRNAs could be detected in more than half of the samples and were included for further analysis. Of them, 20 miRNAs were differently expressed between luminal A-like and control groups, and 12 were different between TNBC and controls. In the contrast between TNBC and luminal A-like breast cancer, we found 34 miRNAs were significantly different, with the most significant miRNA being miR-423 (p = 8.8e-5). The multivariable logistic regression identified a panel of 7 miRNAs which can distinguish TNBC and luminal A-like tumors. ROC analysis found these 7 miRNAs had good discriminatory power (area under ROC curve = 0.865).
Conclusion: Our study demonstrates the existence of a set of circulating miRNAs specific to TNBC, which has a clear “fingerprint” to differentiate TNBC from luminal A-like breast cancer. This finding suggests that early detection markers for different breast cancer subtypes may be distinct. It is also interesting to further investigate if different miRNA profiles in circulation between breast cancer subtypes are derived directly from tumors or from other sources in response to tumors.
Citation Format: Dezheng Huo, Wendy M. Clayton, Toshio F. Yoshimatsu, Jianjun Chen, Olufunmilayo I. Olopade. Breast cancer molecular subtypes are reflected in circulating microRNA profiles. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3995. doi:10.1158/1538-7445.AM2015-3995