Circulating miRNAs.

July 4, 2025 updated by: Cancer Trials Ireland

Novel Breast Cancer Biomarkers and Their Use for Guiding and Monitoring Response to Chemotherapy

To identify a panel of circulating miRNA markers which could help identify those breast cancer patients who are most likely to respond well to neoadjuvant and adjuvant chemotherapy, and indeed serve as an overall prognostic factor and stratify patients into risk categories which would further guide their management. Similarly, the investigators aim to identify a panel of circulating miRNA markers which could monitor patient's response to chemotherapy and hormonal therapies. Ideally a suitable panel of markers would show significant changes in expression level in good-responders whilst little or no change would be observed in miRNA expression in non-responders.

Study Overview

Status

Completed

Conditions

Detailed Description

Primary Objectives:

  1. To identify a panel of miRNAs, detectable in the circulation, which are altered in breast cancer patients
  2. To identify specific combinations of miRNAs ('signatures') which associate with breast cancer intrinsic subtypes, and thereby could aid in prognostication and treatment planning on an individual patient basis.

Secondary Objective:

  1. To determine if systemic miRNA analysis can be used as a biomarker for monitoring response to chemotherapy, in the neoadjuvant setting and in patients who present with breast cancer recurrence and are treated with upfront chemotherapy and/or hormonal therapy.

    This is a prospective cohort studies, involving three study cohorts:

    Cohort 1: All newly diagnosed breast cancer patients who are scheduled to undergo neoadjuvant chemotherapy.

    Cohort 2: All breast cancer patients who present with metastatic disease, disease recurrence or progression, who are commencing up-front chemotherapy +/- hormonal therapy.

    Cohort 3: All breast cancer patients who present with metastatic disease who are commencing hormonal therapy only.

    Blood Sample

    Blood Sampling - Cohort 1:

    - Blood sample 1: at presentation before commencing neoadjuvant treatment.

    - Blood sample 2: midway through their chemotherapy treatment (after 2nd cycle if they are enrolled in a 4 cycle regimen, or after 4th cycle if they are prescribed an 8 week regimen).

    - Blood sample 3: post-chemotherapy (before surgery as applicable).

    - Blood sample 4: 2 to 4 weeks after surgery, or 2 to 4 weeks post 3rd blood sampling if patients do not undergo surgery.

    - Blood sample 5: once during follow-up of 12 to 18 months after surgery or 12 to 18 months post 3rd blood sampling if patients do not undergo surgery.

    Blood Sampling - Cohort 2:

    - Pre-treatment blood sample: at presentation before commencing treatment.

    - On study blood samples: taken at monthly (± 1 week) intervals for a period of 6 months from date of pre-treatment blood sample, despite whether the patient is on treatment or completed treatment.

    On study blood sample 1: 1 month (± 1 week) from date of pre-treatment blood sample

    On study blood sample 2: 2 months (± 1 week) from date of pre- treatment blood sample

    On study blood sample 3: 3 months (± 1 week) from date of pre-treatment blood sample

    On study blood sample 4: 4 months (± 1 week) from date of pre-treatment blood sample

    On study blood sample 5: 5 months (± 1 week) from date of pre-treatment blood sample

    On study blood sample 6: 6 months (± 1 week) from date of pre-treatment blood sample

    - End of study blood sample: once during follow-up of 12 to 18 months from date of pre-treatment blood sample or at the time of disease progression.

    Blood Sampling - Cohort 3:

    - Pre-treatment blood sample: at presentation before commencing treatment.

    - On study blood samples: taken at the following time points despite whether the patient is on treatment or completed treatment.

    On study blood sample 1: 3 months (± 2 weeks) from date of pre-treatment blood sample On study blood sample 2: 6 months (± 2 weeks) from date of pre-treatment blood sample On study blood sample 3: 12 months (± 2 weeks) from date of pre-treatment blood sample

    - End of study blood sample: 18 months (± 2 weeks) from date of pre-treatment blood sample or at the time of disease progression.

    Blood samples will be processed for miRNA analysis, which involves:

1. Lysis using Trizol 2. RNA isolation 3. Assessing concentration and integrity of RNA using Nanodrop spectrophotometry 4. cDNA synthesis (using miRNA specific stem loop primers) 5. PCR amplification and relative quantification (using miRNA specific probes)

Study Type

Observational

Enrollment (Actual)

255

Contacts and Locations

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

Study Locations

  • Ireland
      • Cork, Ireland
        • Bon Secours Hospital
      • Dublin, Ireland
        • Beaumont Hospital
      • Dublin, Ireland
        • St James's Hospital
      • Galway, Ireland
        • University Hospital Galway
      • Letterkenny, Ireland
        • Letterkenny General Hospital
      • Sligo, Ireland
        • Sligo General Hospital
      • Tullamore, Ireland
        • Midlands Regional Hospital Tullamore

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

Sampling Method

Non-Probability Sample

Study Population

Investigators aim to study two populations of breast cancer patients:

  1. Patients undergoing neoadjuvant chemotherapy for breast cancer at tertiary referral breast cancer centres in Ireland.

    For GUH only: Additionally,investigators wish to evaluate miRNA expression levels in patients' diagnostic core biopsies.

  2. Investigators also wish to study the same panel of miRNAs in patients who present with disease recurrence or disease progression, and who are commenced on systemic therapies (hormonal and/or chemotherapy).

Description

Inclusion Criteria

  1. Patient must meet the criteria for either:

    Cohort 1: All patients with a new diagnosis of breast cancer, who are destined to undergo neoadjuvant chemotherapy.

    OR Cohort 2: All breast cancer patients who present with metastatic disease, disease recurrence or progression who will receive up-front chemotherapy ± hormonal therapy.

    OR Cohort 3: All breast cancer patient who present with metastatic disease who are commencing hormonal therapy only.

  2. Patients must be aged 18 years or over.
  3. Patients must be able to give written informed consent.

Exclusion Criteria

All patients, who do not fulfil the inclusion criteria mentioned above.

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
Cohort 1
All newly diagnosed breast cancer patients who are scheduled to undergo neoadjuvant chemotherapy
Cohort 2
All breast cancer patients who present with metastatic disease, disease recurrence or progression, who are commencing up-front chemotherapy ± hormonal therapy
Cohort 3
All breast cancer patient who present with metastatic disease who are commencing hormonal therapy only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between changes in a patients circulating miRNA expression levels over the course of their systemic therapy, and their response to that treatment.
Time Frame: Up to week 66-92

For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.

For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1." For cohort 1, a patient's response to treatment will be determined using 3 standard parameters: clinical, radiological and pathological responses.

For cohort 2 and 3, a patient's response to treatment will be evaluated using RECIST criteria version 1.1."
Up to week 66-92
Correlation of systemic miRNA levels with standard biomarkers of response
Time Frame: Up to week 66-92
Standard bio markers of response include serum CEA and Ca15-3 levels
Up to week 66-92

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relationship between circulating miRNA profiles and patients' intrinsic subtype of breast cancer
Time Frame: Up to week 66-92
Up to week 66-92
Relationship between miRNA expression levels and other existing clinicopathological parameters.
Time Frame: Up to week 66-92
Other existing clinicopathological parameters include: ER, PR and HER2 status, stage of disease,histological grade and size of the tumour, and the Nottingham Prognostic Index.
Up to week 66-92

Collaborators and Investigators

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

Sponsor

Cancer Trials Ireland

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 (Actual)

May 1, 2011

Primary Completion (Actual)

April 1, 2021

Study Completion (Actual)

December 1, 2021

Study Registration Dates

First Submitted

October 24, 2012

First Submitted That Met QC Criteria

November 5, 2012

First Posted (Estimated)

November 7, 2012

Study Record Updates

Last Update Posted (Actual)

July 8, 2025

Last Update Submitted That Met QC Criteria

July 4, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICORG 10-11

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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