Abstract 172P
Background
Breast cancer (BC) is the most common type of cancer in women worldwide. Five-year overall survival has increased to 88%, due to screening programs and better treatment options. Nonetheless, interval cancers (BC diagnosed between routine screening moments) occur, implying that current standards are suboptimal. A possible solution could be to detect biomarkers in biofluids, such as nipple aspirate fluid (NAF). NAF is present in the ductal system of the breast, can be obtained non-invasively, and harbors different biomarkers, including microRNAs (miRNAs). In this study, we evaluated the biomarker potential of miRNAs in NAF for the detection of BC.
Methods
A case-control study was used to assess the differences in miRNA expression between sporadic BC patients (n=116 with successful NAF collection from affected breast) and healthy controls (n=111). A 24 miRNA panel, selected based on literature research and preliminary data, was analysed using real-time quantitative reverse transcription PCR. Logistic regression and ROC analysis were utilized to determine the prediction accuracy of the miRNA panel.
Results
Data from 21 miRNAs resulted in an AUC of >0.8, indicating great diagnostic potential. When overfitting was corrected by cross validation, this AUC drops with ∼0.1. These results indicate that the nipple fluid derived miRNAs are able to differentiate between women with BC and healthy controls. A paired analysis within BC patients was also performed, where the affected breast was compared to the contralateral (unaffected) breast. This analysis showed an AUC of <0.6. Therefore, the affected breast cannot be accurately determined solely using the miRNA panel.
Conclusions
In conclusion, a pre-selected miRNA panel is able to discriminate between NAF samples obtained from BC patients and healthy controls. Assessment of this miRNA panel in NAF could be a promising tool for future (add-on) screening. Therefore, the 21-miRNA panel is currently being assessed in prospectively collected NAF samples from women at increased risk of developing BC. This nested case-control analysis will provide valuable information on the ability of the panel to detect BC in its earliest stages.
Clinical trial identification
CCMO NL57343.041.16; Dutch Trial Register NTR6162/ NL6031: the ORNAMENT study trial: a multicenter, crOss sectional, study to assess microRNA expression in Nipple Aspirate Fluid, blood and tuMor material in women with primary brEast caNcer compared with healthy conTrols. Release data: 12-12-2016 CCMO NL41845.041.12; Dutch Trial Register NL8987: Breast Cancer Biomarkers in Nipple Aspiration Fluid in Healthy Controls. Release data: 12-12-2018.
Legal entity responsible for the study
University Medical Center Utrecht (UMC Utrecht).
Funding
Stichting Vrienden, UMC Utrecht.
Disclosure
All authors have declared no conflicts of interest.