Circulating microRNA 21 Expression Level Before and After Neoadjuvant Systemic Therapy in Breast Carcinoma

NCT ID: NCT05151224

Last Updated: 2021-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

40 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-12-31

Study Completion Date

2024-01-31

Brief Summary

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MicroRNAs (miRNAs) are involved in the development and progression of malignant tumors. In breast cancer, differential miRNA expression has been demonstrated across breast cancer subtypes, with both tumor-promoting and tumor suppressive functions for individual miRNAs.

Novel predictive biomarkers that can be assessed in the liquid specimen before systemic treatment could help to individualize treatment decisions in breast cancer and to potentially avoid ineffective systemic treatment.

In our study we detect level of circulating miRNA 21 in breast cancer patient before and after neoadjuvant treatment , whether there will be change or not, and if related to complete pathological response.

Detailed Description

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MicroRNAs (miRNAs) are a group of non-coding, single stranded RNAs of \~ 19-24 nucleotides, which act by a novel mechanism of posttranscriptional regulation that is profoundly altered in malignant cells. (Ling, Fabbri and Calin, 2013).Based on the function of miRNAs, they are divided into two types: an oncomir, implicated in cancer progression by regulating tumor suppressor genes negatively; and a tumor suppressor, preventing cancers by regulating oncogenes. (Zhang et al., 2007).

A key oncomir in carcinogenesis is miRNA-21, which was one of the first miRNAs detected in the human genome. It is located on chromosome 17 in the tenth intron of the coding gene transmembrane protein 49, which targets various tumor suppressors like PTEN, PDCD4, p53, and TAp63 pathways. (Yadav et al., 2016)

Experimental and literature research has highlighted that miRNA-21 was always significantly elevated in every study that included invasive breast carcinomas compared with healthy breast tissue. (Petrović, 2016).

miRNA-21 has been shown to be a very important promoter of cellular outgrowth, migration, invasion, and metastasis. In breast carcinoma cell lines, miRNA-21 was connected to cell proliferation and migration. (Yan et al., 2011).

Mei and her colleagues (2010) reported that miRNA-21 up-regulation is associated with therapy (taxol) resistance in breast cancer cells and further validated in a recent study by (Chen and Bourguignon, 2014) in which miRNA-21 up-regulation resulted in an increase of anti-apoptosis protein BCL-2 and chemo-resistance in breast cancer cells

Various studies have supported the potential role of circulating miRNAs to be used as prognostic and predictor biomarkers in breast cancer. (Schwarzenbach, 2017)

In their analysis of the blood serum of 56 breast cancer patients, Wang et al. (2012) illustrate reduced miR-125b levels to correlate with resistance to four cycles of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC). Another recent study investigating dynamic changes of circulating miRNA as indicator for clinical response for neoadjuvant chemotherapy in HER2 negative patients , found that dynamics of three plasma miRNA , including miRNA 222, miRNA 20-a and miRNA 451 was associated with chemosensitivity. (Zhu et al., 2018)

The expression of serum-miRNA-125b and the changes of serum miRNA-21 expression during neoadjuvant chemotherapy were associated with chemotherapy response and disease-free survival (DFS). (Liu et al., 2017). Yadav et al. (2016) found that breast cancer patients received neoadjuvant therapy shows significant impact on overall reduction in serum miRNA-21 expression compared to before therapy (p \< 0.0001)

Conditions

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Breast Carcinoma

Keywords

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breast, microRNA 21, Neoadjuvant thera[py

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Breast cancer patients eligible to neoadjuvant systemic therapy

Invasive breast cancer, age are 18 years or more, from stage IIB to stage IIIC, all subtypes are included, either HR (ER, PR) positive or negative, HER2 positive or negative, eligible to neoadjuvant systemic therapy.

microRNA 21

Intervention Type DIAGNOSTIC_TEST

Plasma microRNA 21 5p expression, by real-time polymerase chain reaction, before and after neoadjuvant systemic therapy.

Blood sample will be taken by a trained nurse, amount of blood will be 3 ml, and will be taken twice, one time before the start of the neoadjuvant systemic treatment , second time by the end of the neoadjuvant systemic treatment.

Interventions

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microRNA 21

Plasma microRNA 21 5p expression, by real-time polymerase chain reaction, before and after neoadjuvant systemic therapy.

Blood sample will be taken by a trained nurse, amount of blood will be 3 ml, and will be taken twice, one time before the start of the neoadjuvant systemic treatment , second time by the end of the neoadjuvant systemic treatment.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Age \>/= 18 years old.
* Breast cancer diagnosis histologically proven and pathology report from breast and ipsilateral axillary nodes.
* Pathology: invasive carcinoma.
* Staging: tumor size \>2cm (\>/=T2), node positive (N \>/= 1), i.e. \>/= T2N1; from stage IIB to stage IIIC, according to AJCC breast Cancer staging 8th edition. (Giuliano, Edge and Hortobagyi, 2018)
* All subtypes are included, either HR (ER, PR) positive or negative, HER2 positive or negative.
* Neoadjuvant systemic treatment composed of anthracyclines-based chemotherapy and taxanes, trastuzumab for HER2 positive patients

Exclusion Criteria

* Metastatic breast cancer
* inflammatory breast cancer,
* male breast cancer,
* bilateral breast cancer, or concurrent malignancy
* Previous malignancy.
* Presence of any contraindication to neoadjuvant treatment
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Ain Shams University

OTHER

Sponsor Role lead

Responsible Party

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Ebtehal Mohamed Mahmoud Salah

Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ebtehal M Salah

Role: PRINCIPAL_INVESTIGATOR

Assistant lecturer of clinical oncology

Iman Sharawy

Role: STUDY_DIRECTOR

Professor of clinical oncology

Locations

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Ain Shams University Hospitals

Cairo, , Egypt

Site Status

Countries

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Egypt

Central Contacts

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Ebtehal M Salah, MD

Role: CONTACT

Phone: +201013678565

Email: [email protected]

Iman A Sharawy, Phd

Role: CONTACT

Phone: +201068280224

Email: [email protected]

Facility Contacts

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Ebtehal M Salah

Role: primary

References

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Mei M, Ren Y, Zhou X, Yuan XB, Han L, Wang GX, Jia Z, Pu PY, Kang CS, Yao Z. Downregulation of miR-21 enhances chemotherapeutic effect of taxol in breast carcinoma cells. Technol Cancer Res Treat. 2010 Feb;9(1):77-86. doi: 10.1177/153303461000900109.

Reference Type RESULT
PMID: 20082533 (View on PubMed)

Yadav P, Mirza M, Nandi K, Jain SK, Kaza RC, Khurana N, Ray PC, Saxena A. Serum microRNA-21 expression as a prognostic and therapeutic biomarker for breast cancer patients. Tumour Biol. 2016 Nov;37(11):15275-15282. doi: 10.1007/s13277-016-5361-y. Epub 2016 Sep 30.

Reference Type RESULT
PMID: 27696295 (View on PubMed)

Ling H, Fabbri M, Calin GA. MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 2013 Nov;12(11):847-65. doi: 10.1038/nrd4140.

Reference Type RESULT
PMID: 24172333 (View on PubMed)

Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007 Feb 1;302(1):1-12. doi: 10.1016/j.ydbio.2006.08.028. Epub 2006 Aug 16.

Reference Type RESULT
PMID: 16989803 (View on PubMed)

Petrovic N. miR-21 Might be Involved in Breast Cancer Promotion and Invasion Rather than in Initial Events of Breast Cancer Development. Mol Diagn Ther. 2016 Apr;20(2):97-110. doi: 10.1007/s40291-016-0186-3.

Reference Type RESULT
PMID: 26891730 (View on PubMed)

Yan LX, Wu QN, Zhang Y, Li YY, Liao DZ, Hou JH, Fu J, Zeng MS, Yun JP, Wu QL, Zeng YX, Shao JY. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth. Breast Cancer Res. 2011 Jan 10;13(1):R2. doi: 10.1186/bcr2803.

Reference Type RESULT
PMID: 21219636 (View on PubMed)

Chen L, Bourguignon LY. Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer. 2014 Mar 8;13:52. doi: 10.1186/1476-4598-13-52.

Reference Type RESULT
PMID: 24606718 (View on PubMed)

Schwarzenbach H. Clinical Relevance of Circulating, Cell-Free and Exosomal microRNAs in Plasma and Serum of Breast Cancer Patients. Oncol Res Treat. 2017;40(7-8):423-429. doi: 10.1159/000478019. Epub 2017 Jun 28.

Reference Type RESULT
PMID: 28683441 (View on PubMed)

Zhu W, Liu M, Fan Y, Ma F, Xu N, Xu B. Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer. Cancer Med. 2018 Sep;7(9):4420-4433. doi: 10.1002/cam4.1723. Epub 2018 Aug 11.

Reference Type RESULT
PMID: 30099860 (View on PubMed)

Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z, Luo H. Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012;7(4):e34210. doi: 10.1371/journal.pone.0034210. Epub 2012 Apr 16.

Reference Type RESULT
PMID: 22523546 (View on PubMed)

Liu B, Su F, Chen M, Li Y, Qi X, Xiao J, Li X, Liu X, Liang W, Zhang Y, Zhang J. Serum miR-21 and miR-125b as markers predicting neoadjuvant chemotherapy response and prognosis in stage II/III breast cancer. Hum Pathol. 2017 Jun;64:44-52. doi: 10.1016/j.humpath.2017.03.016. Epub 2017 Apr 12.

Reference Type RESULT
PMID: 28412211 (View on PubMed)

Other Identifiers

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FMASUMD232/2021

Identifier Type: -

Identifier Source: org_study_id