No. | Clinical Study | Endpoints | Source | Samples | Method of detection | Biomarkers | Ref |
---|---|---|---|---|---|---|---|
1. | CTC-specific miRNAs | Enhance the prognostic accuracy of CTCs in MBC | LB – CTCs (peripheral blood) | MBC with CTC ≥5/7.5 mL (n = 16); patients with CTC = 0/7.5 mL (n = 16) and healthy donors (n = 8) | CellSearch system for CTC detection | ⬆ CTC-specific miR-106b; ⬆ E-cadherin; ⬆ vimentin | [65] |
2. | Clinical Trials NCT00433511 | CTCs to predict late clinical recurrence in HER2- BC | LB – CTCs (peripheral blood) | 547 Lymph Node Positive and High Risk Lymph Node Negative BC | CellSearch system for CTC detection | higher recurrence risk is associated with higher CTC burden. | [75] |
3. | The LiqBreasTrack cohort study (Nov 2016-Feb 21) | Progression-free survival (PFS) between the first T-DM1 administration and progressive disease or last follow-up. | LB – ctDNA (plasma) | 28 BC tissues (n = 14); 337 plasma (n = 20) | Targeted NGS and dPCR | ⬆ MYC/FGFR1/ESR1 amplifications; ⬇ HER2 amplifications; ⬇ PIK3CA mutations | [79] |
4. | Long non-coding RNAs | Diagnosis of early stage BC and patients with larger tumors (> 2 cm) | LB – lincRNA:miRNA (blood) | 25 controls and 70 BC patients | q-PCR | ⬆ LINC00511 and onco-miR-301a-3p; ⬇ miR-185-3p | [92] |
5. | Circulating microRNAs | Predict the CTC status of patients with MBC | LB –Ct miRNAs (plasma) | 269 samples (61 CTC-positive, 72 CTC-negative, 60 CTC-low MBC cases, and 76 controls) | TaqMan Human MicroRNA array | ⬆ miR-141, miR-200a, miR-200b, miR-200c, miR-203, miR-210, miR-375, and miR-801 upregulated in CTC+ MBC; ⬇ miR-768-3p in MBC; | [99] |
6. | SUCCESS A trial – MicroRNAs as prognostic markers in post-operative EBC patients | Associate whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-op EBC patients | LB – whole blood (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up) | 48 post-operative patients; 17 female healthy donors as negative controls | miRNA quantitative PCR | ⬆ miR-19a, miR-22 and miR-127 in EBCs; ⬆ miR-127 correlated with the presence of CTCs | [101] |
7. | Precursor miRNAs of oncomiRs (miR526b and miR655) | Differentiate malignant tumors from benign lesions | LB – pri-miRNA (plasma) | 90 malignant tumors; 20 benign lesions (control) | q-PCR | ⬆ pri-miR526b and pri-miR655 in Stage I plasma and malignancy | |
8. | 4-circulatory miRNA signature in plasma of EBC | Early detection of (ER/PR+) IDC-BC from healthy controls | LB – miRNAs (plasma) | 41 early invasive ductal carcinoma (IDC) Lebanese BC patients; 32 healthy controls | miRNA quantitative PCR | ⬆ miR-145, miR-139-5p, miR-425-5p, and miR-130a upregulated in EBC plasma | [106] |
9. | 5-miRNA signature | Discern high- and low-risk of relapse (early recurrence and those with no recurrence) in post-operative BC patients | MiRNAs - Tumor (tissue sample) | 71 primary BC (group A – disease-free); (group B - early relapse); (group C - late relapse) | Microarray and RT-qPCR validation | ⬇ miR-149, miR-10a, miR-20b, miR-30a-3p and miR-342-5p in high-risk, early recurrence group | [108] |
10. | Exosomal miRNAs | Diagnostic markers for BC | LB – miRs (plasma) | 16 healthy plasma and 16 BC plasma | NGS, q-PCR | ⬆ miR-1246 and miR-21 | [117] |
11. | Exosomal miRNAs | Diagnostic markers for BC subtypes | LB – miRs (serum) | Control (n-16); LA (n-16); TNBC (n-16) | RNA-seq; q-PCR | ⬆ miR-142-5p, miR-320a and miR-4433b-5p | [118] |
12. | Exosomal miRNAs | The diagnostic role of miR-106a-363 cluster in BC | LB - miRs (plasma, serum) | (400 plasma) - 200 BC patients and 200 healthy controls (HCs); (406 serum) - 204 BC patients and 202 HCs | q-PCR | ⬆ plasma miRNAs (miR-106a-3p, miR-106a-5p, miR-20b-5p, miR-92a-2-5p); ⬆ serum miRNAs (miR-106a-5p, miR-19b-3p, miR-20b-5p, and miR-92a-3p) | [119] |
13. | Circulating miRNAs | Diagnosis of early BC | LB - miRs (plasma) | 65 BC patients and 34 HCs | real-time PCR (RQPCR) | ⬆ miR-99a, miR-130a, miR-484 and miR-1260a | [121] |
14. | Circulating miRNAs | Early detection markers for breast cancer | LB – miRs (plasma) | 127 sporadic breast cancer cases and 80 healthy controls | TaqMan low-density arrays (TLDA) and qPCR) | ⬆ miR-148b, miR-409-3p and miR-801 | [122] |
15. | Circulating miRNAs | Detect malignant from benign pre-treatment plasma of BC | LB – miRs (plasma) | Benign - 40; Non-metastatic BC – 54; Metastatic BC - 14 | Microarray | ⬆ hsa-miR-652-5p | [123] |
16. | Circulating miRNAs | Early stage BC | LB – miRs (blood) | 83 BC patients; 63 Healthy controls | real-time PCR (RQPCR) | ⬆ miR-195 | [124] |
17. | Circulating miRNAs | Early stage BC | LB – miRs (serum) | 210 BC patients; 102 Healthy controls | real-time PCR (RQPCR) | ⬆ miR-195 | [125] |
18. | Circulating Biomarkers (miRNA+ protein) | ER+ BC to Bone metastasis | LB – exosomal miRs (blood) | 23 ER+ BC patients; 22 healthy donors | Microarray; Western blot | ⬆ exosomal miR-19a and Integrin-Binding Sialoprotein (IBSP) | [130] |
19. | The NeoALTTO Study cohort | Pathological complete response (pCR) to single agent trastuzumab-based neoadjuvant therapy (NAC). | LB – miRs (plasma) | 52 BC patients; 752 microRNAs | PCR assay | ⬆ ct-miR-148a-3p, ⬆ ct-miR-374a-5p; ⬆ ct-miR-140-5p | [131] |
20. | TNBC Exosomal miRs | Identify refractory and poor NAC responders | LB – miRs (Blood) | 200 BC patients | droplet digital PCR (ddPCR) | ⬇ miR-185, miR-4283, miR-5008, miR-3613; ⬆ miR-1302, miR-4715, miR-3144 | [132] |
21. | Circulatory miRNAs | Detect early stage BC | LB – miRs (serum) | 1280 BC serum; 2836 non-cancer control; 63 non-breast benign samples | Microarray | ⬆ miR-1246, miR-1307-3p, miR-4634, miR-6861-5p and miR-6875-5p) | [133] |
22. | SUCCESS trial | Association of plasma miRs and BC invasiveness | LB – miRs (plasma) | 111 BC patients (pre & post chemo); 46 Healthy controls | q-PCR | ⬆ miR-16, miR-27a and miR-132 (pre-chemo); ⬇ miR-27a and miR-132 (post-chemo); ⬆ miR-107 (ER- tumors) | [134] |
23. | Circulating biomarker (miRNAs + proteins) | Prognostic biomarkers of BC | LB – miRs; proteins (plasma) | 30 BC patients; 10 HCs; 253 BC plasma samples | droplet digital PCR (ddPCR) | ⬆ miR-923 and CA 15–3 | [135] |
24. | Circulating tumor cells (CTCs) and serum exosomal miRNAs | Diagnostic and predictive biomarkers of relapse post-NAC | LB – CTCs; miRs (serum) | 53 post-NAC BC patients; 8 HCs; 6 metastatic patients from the NAC cohort | qPCR | ⬆ miRNA-21, miRNA-222 and miRNA-155 correlate with CTCs in Metastatic patients | [136] |