MicroRNAs detect breast cancer in nipple aspirate fluid: results from a Dutch multicenter cross-sectional study

Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths in women worldwide. Novel (personalized) treatments and detection as early as possible are key to improving prognosis. We hypothesized that microRNA (miRNA) levels in nipple aspirate fluid (NAF) can be used to detect breast cancer. NAF samples were acquired from 135 breast cancer patients and 114 healthy controls using a non-invasive collection method. miRNA levels were analyzed with quantitative polymerase chain reaction using Taqman Advanced miRNA assays. The discriminative value of a 20-miRNA NAF panel for breast cancer detection was evaluated with LASSO regression and cross-validation. Six individual miRNAs demonstrated significant odds ratio ranging between 0.86-1.38. After LASSO regression with cross-validation, a 20-miRNA panel resulted in an area under the curve (AUC) of 0.70. A second analysis, where within women the affected breast was compared to the contralateral breast, resulted in an AUC of 0.54. A 20-miRNA panel in NAF is able to discriminate between breast cancer patients and healthy controls. With a moderate discriminative value (after cross-validation) and little discomfort, our method shows promise for future personalized screening applications. One group that can especially benefit from this personalized strategy is women with dense breasts, where a positive miRNA test could stratify for supplemental MRI. Future studies are still necessary to determine if early stage detection is possible using the miRNA panel. CCMO NL57343.041.16, Dutch Trial Register NTR6162/NL6031, Registered 17 August 2016, https://onderzoekmetmensen.nl/nl/trial/50271 ; CCMO NL 41845.041.12​, Dutch Trial Register NL8987, Registered 20 February 2013, https://onderzoekmetmensen.nl/nl/trial/47370