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

November 27, 2021 updated by: Ebtehal Mohamed Mahmoud Salah, Ain Shams University

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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)

Study Type

Observational

Enrollment (Anticipated)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Invasive breast cancer, from stage IIB to stage IIIC, all subtypes are included, who are candidates for neoadjuvant systemic therapy.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Describe miRNA 21 expression level before and after neoadjuvant systemic therapy in breast cancer patient.
Time Frame: 1 year
miRNA 21 expression level before and after neoadjuvant systemic therapy
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure relation between miRNA 21 expression level before and after neoadjuvant systemic therapy and pathological response.
Time Frame: 1 year
Relation between miRNA 21 expression level before and after neoadjuvant systemic therapy and pathological response
1 year
Measure relation between the miRNA 21 expression and the clinicopathological parameters of Breast Cancer patients.
Time Frame: 1 year
Relation between the miRNA 21 expression and the clinicopathological parameters
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Investigators

  • Principal Investigator: Ebtehal M Salah, Assistant lecturer of clinical oncology
  • Study Director: Iman Sharawy, Professor of Clinical Oncology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2021

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

January 1, 2024

Study Registration Dates

First Submitted

November 27, 2021

First Submitted That Met QC Criteria

November 27, 2021

First Posted (Actual)

December 9, 2021

Study Record Updates

Last Update Posted (Actual)

December 9, 2021

Last Update Submitted That Met QC Criteria

November 27, 2021

Last Verified

November 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FMASUMD232/2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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