Abstract
Simple SummaryIn population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. A retrospective cohort of plasma samples divided into training and testing sets and a prospective cohort of women with suspicious imaging findings who underwent tissue biopsy were investigated through a global microRNA profile by OpenArray. Seven signatures, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were identified and validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 of them were confirmed in the prospective cohort.In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.
Highlights
Breast cancer (BC) is the most frequent cancer among women, and despite screens for its early diagnosis, it remains a leading cause of cancer-related mortality worldwide [1]
Of the 144 TRS plasma samples that were profiled on the OpenArray plates, 105 (46 healthy donors (HD), 31 T, and 28 B) passed the preprocessing steps, and 255 miRNAs were considered in subsequent statistical analyses (Figure 1)
Hemolysis-free miRNAs that were associated with disease status (T vs. HD or B vs. HD) were identified by univariate analysis by Kruskal–Wallis test
Summary
Breast cancer (BC) is the most frequent cancer among women, and despite screens for its early diagnosis, it remains a leading cause of cancer-related mortality worldwide [1]. The Breast Imaging Report and Data System (BI-RADS) lexicon was introduced by the American College of Radiology to score the risk of suspected BC in imaging studies [2,3] and determine the need for image-guided biopsy. BI-RADS categories 4 and 5 classify suspicious lesions for which biopsy is recommended. While BI-RADS 5 findings are greatly suggestive of BC, BI-RADS 4 lesions are highly variable in the outcome group, having a probability of malignancy ranging from 3% to 95%. Some patients have benign lesions but undergo unnecessary biopsies or, in some cases, surgery. Biopsy remains required to prove that suspicious imaging findings are malignant or benign in 7% to 10% of women who undergo breast cancer screens, as reported by the National Centre for screening monitoring (https://www.osservatorionazionalescreening.it/, accessed on 9 August 2021)
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