Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy

Abstract

BackgroundBreast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients.MethodsFifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR.ResultsBefore neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells.ConclusionLiquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis.Electronic supplementary materialThe online version of this article (10.1186/s13058-019-1109-0) contains supplementary material, which is available to authorized users.

Extracellular vesicle-miRNAs as liquid biopsy biomarkers for disease identification and prognosis in metastatic colorectal cancer patients

“…CTCs are implicated in disease dissemination and they have been proposed as indicators of minimal residual disease 41 , which cannot be detected by standard imaging methodologies in the clinical practice 42,43 . miRNAs profiles have been related to the metastatic spread of the tumour, characterized by the presence of CTCs 44 . However, the methods for CTCs identification have not been completely standardized, including several expensive and time-consuming isolation and characterization protocols 45 .…”

A Circulating miRNA Signature for Stratification of Breast Lesions among Women with Abnormal Screening Mammograms

“…Mammography is the current gold standard for breast cancer screening; however, this modality produces false-negatives and also has high false-positive rates [1][2][3][4][5]. According to a study in the United States (U.S.), out of all screening mammograms (n = 702,154), approximately 24.5% (n = 171,829) were found to be abnormal, with 2,599 women diagnosed with ductal carcinoma in situ (DCIS) or invasive breast cancer [1].…”

Prognostic and Clinicopathological Significance of MiR-155 in Breast Cancer: A Systematic Review

“…Differently from previous findings, no predictive value for miR-155 was found after neoadjuvant chemotherapy treatment [27]. Finally, recently, Rodriguez-Martinez and colleagues [33] proposed the use of exosomal miRNAs and circulating tumour cells as diagnostic and predictive biomarkers in BC patients under neoadjuvant treatment. They demonstrated a positive correlation between miR-155 expression and the number of circulating tumour cells (CTCs) ≥ 3CTCs/10 mL at diagnosis.…”