Breast CancerIMAGENCT02327572
Age-related Changes in the Immune System and Their Impact on Elderly Breast Cancer
An observational study of Breast Cancer, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
This research project aims to study this intriguing relationship between ageing and breast cancer biology, and more specifically the changes that occur within the tumor microenvironment with increasing age. Read more about this study
- Who is it for?
- Ages 35 years and older, women only
- Conditions the study is for
- Breast Cancer
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- Mar 2014to Jul 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: * Patients newly diagnosed with breast cancer who will undergo surgery and gave written informed consent * Group 1 : 30 patients aged 70+ Group 2 : 15 patients aged 55-65 (post-menopausal) Group 3 : 15 patients aged 35-45 (pre-menopausal) * Tumor selection : grade II/III invasive tumor, any histological type, ER-positive, HER2-negative * Tumor size ≥1.5 cm (clinical assessment: mammoechography and/or clinical examination) * Routine geriatric assessment performed prior to surgery in group 1.
Who may be able to join
- o Patients newly diagnosed with breast cancer who will undergo surgery and gave written informed consent
- Group 1 : 30 patients aged 70+ Group 2 : 15 patients aged 55-65 (post-menopausal) Group 3 : 15 patients aged 35-45 (pre-menopausal)
- Tumor selection : grade II/III invasive tumor, any histological type, ER-positive, HER2-negative
- Tumor size ≥1.5 cm (clinical assessment: mammoechography and/or clinical examination)
Who cannot join
- -
Trial locations and contacts
1 site in 1 country.
About this study
This research project aims to study this intriguing relationship between ageing and breast cancer biology, and more specifically the changes that occur within the tumor microenvironment with increasing age. Furthermore, it will focus on the link between these microenvironmental changes and organismal ageing (as measured by chronological age, geriatric evaluation of elderly patients, and circulating biomarkers of ageing), since it seems logical that age-related changes in the stromal part of a tumor (fibroblasts, immune cells, endothelial cells, fatty cells, …i.e. host cells) are due to the ageing process of the entire body. Most particularly, the amount and type of infiltrating immune cells might reflect the degree of immunosenescence of the host. More and more research points out the crucial role of the immune system in tumorigenesis and progression, and, at the same time, the immune system is one of the most affected components in the process of ageing. .
Read the detailed description
Despite the high relevance of ageing/immunosenescence and frailty in oncogeriatric practice, immuno-senescence markers have so far not been considered in concert with clinical tumor characteristics and the profile of tumor infiltrating leukocytes. In the proposed project, the investigators will examine immunosenescence markers in blood and characterize the leukocyte infiltrate in the tumor microenvironment in the setting of elderly breast cancer.
The main goal of this project is thus to investigate the relation and interaction between the following 3 aspects:
(i) immune status of the host: chronological age and immunosenescence in peripheral blood; (ii) tumor microenvironment: local immune response (evaluated via assessment of the amount and nature of tumor infiltrating leukocytes [TIL]); (iii) clinical tumor characteristics: tumor size, grade, receptor status, lymph node involvement.
To realize this project, the investigators will set up a prospective clinical study comprising three distinct age categories of breast cancer patients and integrating a variety of immunosenescence markers. Different specific manifestations of immune system ageing will be studied : age-related pro-inflammatory status (inflammageing), increased expression of the senescence marker p16INK4a in T lymphocytes, shifts in subset composition of the PBMC pool, age-associated changes in expression of immune-related genes in PBMC and altered abundance of specific ageing-related plasma microRNAs.
At the tumor microenvironmental level, the leukocyte infiltrate will be studied in detail. The profile of tumor-infiltrating immune cells will be compared between the distinct age groups and will be correlated to systemic markers of ageing/immunosenescence (in blood) and tumor biology, most particularly lymph node involvement.
Concrete research questions:
- How are the different immunosenescence markers (i.e. subset profile of PBMC, pro-inflammatory markers in plasma, lymphocyte senescence as evidenced by p16INK4a expession in T lymphocytes, expression of immune-related genes in PBMC and abundance of ageing-related circulating microRNAs) correlated with each other and with the patient's calendar age?
- Does the local immune response in the tumor (amount and nature of TIL) correlate with the different immunosenescence markers?
- Is there a relationship between tumor biology, most particularly lymph node involvement, and the local immune response in the tumor ?
With this study, the investigators intend to improve our fundamental understanding of age-related changes in general immune status and tumor-specific immune responses and their impact on tumor progression. This may add to recent advances in newly emerging therapeutic strategies, such as immune-related approaches. Due to recent advances in biology and genomics, it has become possible to personalize an individual's cancer treatment based on molecular tumor characteristics. In the elderly, however, host factors also become increasingly important and may influence both tumor behavior/progression and therapy tolerance/response. Therefore, a better understanding of the biological mechanisms underlying ageing/immunosenescence, its association with cancer and the potential prognostic/predictive information that the patient's ageing/immunosenescence profile can provide is mandatory.
- Conditions
- Breast Cancer
- Medical subject headings
- Breast Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
- Are there differences in tumor stroma, both with regard to immune infiltration and cellular senescence, between young and old patients, and between old fit and old frail patients?
Measured: at diagnosis
Secondary outcomes (3)
- Does the local immune response in the tumor (amount and type of infiltrating cells) correlate with subset profile of circulating immune cells (PBMC) and immunosenescence markers in the plasma, and with clinical ageing?
Measured: at diagnosis
- Is there a relation between senescence markers expressed in tumor stroma (SAβ-galactosidase, heterochromatinisation, SASP) and ageing markers measured in the blood?
Measured: at diagnosis
- Do immune infiltration of the tumor, stromal senescence in the tumor and plasma ageing/immunosenescence profile correlate with relapse and survival (long term outcome)?
Measured: at diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2014 (estimated)
- Study startMar 2014
- Primary completionJun 2015
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, prof. dr. Hans Wildiers, Universitaire Ziekenhuizen KU Leuven
- Investigators
- hans wildiers, Study chair, department of general medical oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02327572
- Sponsor's protocol ID
- S56278 UGasthuisberg
- Other IDs
- S56278
- Acronym
- IMAGE
- Status last verified
- Oct 2016
- First submitted
- 8 Dec 2014
- Last updated
- 25 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Age-related Changes in the Immune System and Their Impact on Elderly Breast Cancer
- ClinicalTrials.gov ID
- NCT02327572
- Acronym / sponsor ID
- IMAGE / S56278 UGasthuisberg
- Conditions
- Breast Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 30 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research project aims to study this intriguing relationship between ageing and breast cancer biology, and more specifically the changes that occur within the tumor microenvironment with increasing age. Furthermore, it will focus on the link between these microenvironmental changes and organismal ageing (as measured by chronological age, geriatric evaluation of elderly patients, and circulating biomarkers of ageing), since it seems logical that age-related changes in the stromal part of a tumor (fibroblasts, immune cells, endothelial cells, fatty cells, …i.e. host cells) are due to the ageing process of the entire body. Most particularly, the amount and type of infiltrating immune cells might reflect the degree of immunosenescence of the host. More and more research points out the crucial role of the immune system in tumorigenesis and progression, and, at the same time, the immune system is one of the most affected components in the process of ageing. .
Detailed description
Despite the high relevance of ageing/immunosenescence and frailty in oncogeriatric practice, immuno-senescence markers have so far not been considered in concert with clinical tumor characteristics and the profile of tumor infiltrating leukocytes. In the proposed project, the investigators will examine immunosenescence markers in blood and characterize the leukocyte infiltrate in the tumor microenvironment in the setting of elderly breast cancer.
The main goal of this project is thus to investigate the relation and interaction between the following 3 aspects:
(i) immune status of the host: chronological age and immunosenescence in peripheral blood; (ii) tumor microenvironment: local immune response (evaluated via assessment of the amount and nature of tumor infiltrating leukocytes [TIL]); (iii) clinical tumor characteristics: tumor size, grade, receptor status, lymph node involvement.
To realize this project, the investigators will set up a prospective clinical study comprising three distinct age categories of breast cancer patients and integrating a variety of immunosenescence markers. Different specific manifestations of immune system ageing will be studied : age-related pro-inflammatory status (inflammageing), increased expression of the senescence marker p16INK4a in T lymphocytes, shifts in subset composition of the PBMC pool, age-associated changes in expression of immune-related genes in PBMC and altered abundance of specific ageing-related plasma microRNAs.
At the tumor microenvironmental level, the leukocyte infiltrate will be studied in detail. The profile of tumor-infiltrating immune cells will be compared between the distinct age groups and will be correlated to systemic markers of ageing/immunosenescence (in blood) and tumor biology, most particularly lymph node involvement.
Concrete research questions:
- How are the different immunosenescence markers (i.e. subset profile of PBMC, pro-inflammatory markers in plasma, lymphocyte senescence as evidenced by p16INK4a expession in T lymphocytes, expression of immune-related genes in PBMC and abundance of ageing-related circulating microRNAs) correlated with each other and with the patient's calendar age?
- Does the local immune response in the tumor (amount and nature of TIL) correlate with the different immunosenescence markers?
- Is there a relationship between tumor biology, most particularly lymph node involvement, and the local immune response in the tumor ?
With this study, the investigators intend to improve our fundamental understanding of age-related changes in general immune status and tumor-specific immune responses and their impact on tumor progression. This may add to recent advances in newly emerging therapeutic strategies, such as immune-related approaches. Due to recent advances in biology and genomics, it has become possible to personalize an individual's cancer treatment based on molecular tumor characteristics. In the elderly, however, host factors also become increasingly important and may influence both tumor behavior/progression and therapy tolerance/response. Therefore, a better understanding of the biological mechanisms underlying ageing/immunosenescence, its association with cancer and the potential prognostic/predictive information that the patient's ageing/immunosenescence profile can provide is mandatory.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 35 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- * Patients newly diagnosed with breast cancer who will undergo surgery and gave written informed consent * Group 1 : 30 patients aged 70+ Group 2 : 15 patients aged 55-65 (post-menopausal) Group 3 : 15 patients aged 35-45 (pre-menopausal) * Tumor selection : grade II/III invasive tumor, any histological type, ER-positive, HER2-negative * Tumor size ≥1.5 cm (clinical assessment: mammoechography and/or clinical examination) * Routine geriatric assessment performed prior to surgery in group 1.
Key inclusion criteria (4 listed)
- o Patients newly diagnosed with breast cancer who will undergo surgery and gave written informed consent
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
- Are there differences in tumor stroma, both with regard to immune infiltration and cellular senescence, between young and old patients, and between old fit and old frail patients?
Time frame: at diagnosis
3 secondary outcomes
- Does the local immune response in the tumor (amount and type of infiltrating cells) correlate with subset profile of circulating immune cells (PBMC) and immunosenescence markers in the plasma, and with clinical ageing?
Time frame: at diagnosis
- Is there a relation between senescence markers expressed in tumor stroma (SAβ-galactosidase, heterochromatinisation, SASP) and ageing markers measured in the blood?
Time frame: at diagnosis
- Do immune infiltration of the tumor, stromal senescence in the tumor and plasma ageing/immunosenescence profile correlate with relapse and survival (long term outcome)?
Time frame: at diagnosis
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
hans wildiers study chair
department of general medical oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
- Are there differences in tumor stroma, both with regard to immune infiltration and cellular senescence, between young and old patients, and between old fit and old frail patients? (time frame: at diagnosis). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2016.