Abstract A54: Circulating miR-15a, miR-101, and miR-144 to distinguish between benign and malignant breast lesions in women with BI-RADS 4 mammography

Abstract

Abstract BI-RADS 4 category reports suspicious breast lesions in mammograms, which have 23-34% chance of malignancy and require core biopsies for diagnosis confirmation. New biomarkers are needed and have been sought to improve diagnose in those patients. Once the human plasma contains a large number of circulating microRNAs (miRNAs), variations in their circulating levels have been associated with pathologic conditions, including cancer. We hypothesized that miRNA circulating level can be used to separate malignant from benign breast lesions in BI-RADS 4 patients. In this context, here we compared the circulating levels of 1,805 miRNAs in cancer patients (BI-RADS 5 or 6 mammography) and controls (BI-RADS 1 or 2 mammography) using miRNome PCR array to identify cancer-associated alterations in circulating miRNA levels. miRNAs with altered circulating levels in cancer patients were validated by qRT-PCR in an independent cohort and then investigated as biomarkers to distinguish between benign and malignant breast lesions in women with BI-RADS 4 mammography. We identified 12 miRNAs with different circulating levels (>1.5x and a p-value < 0.05) between controls and cancer patients. Altered circulating levels for 3 of these miRNAs (miR-15a, miR-101, and miR-144) were validated in an independent cohort of cancer patients. Next, we investigated the level of those three miRNAs in BI-RADS 4 patients and constructed an artificial neural network to test the capacity of this miRNA circulating profile to detect malignant breast lesions in women with BI-RADS 4 mammography. We found that the circulating levels of miR-15a, miR-101, and miR-144 were efficient to distinguish benign from malignant breast lesion with 92% of accuracy. In this work, we demonstrated how miRNAs circulating levels can be used as biomarkers to distinguish between benign and malignant breast lesions in women with BI-RADS 4 mammography and concluded that circulating miRNAs can be useful to improve breast cancer diagnosis. Citation Format: Julia Alejandra Pezuk, Thiago Luiz Araujo Miller, José Luiz Barbosa Bevilacqua, Alfredo Carlos Simões Barros, Felipe Eduardo Martins de Andrade, Luiza Freire de Andrade e Macedo, Amanda Natasha Menardo Claro, Anamaria Aranha Camargo, Pedro Alexandre Favoretto Galante, Luiz Fernando Lima Reis. Circulating miR-15a, miR-101, and miR-144 to distinguish between benign and malignant breast lesions in women with BI-RADS 4 mammography [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A54.