Locally Advanced Breast CancerCyto-CogNCT00756132
Using Bio Markers to Predict Disease Recurrence and Cognitive Function in High Risk Breast Ca
An observational study of Locally Advanced Breast Cancer and Breast Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Women with breast cancer undergo treatments that decrease the chance of recurrence of cancer, but are associated with several side effects, including declines in memory and attention and other thinking abilities. The causes of these declines are not known. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Locally Advanced Breast Cancer, Breast Cancer
- How many people
- 120 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2008to Sep 2017
- 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 18 to 65 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Women ages 18-65 with a newly diagnosed locally advanced breast cancer and healthy women ages 18-65.
Who may be able to join
- (i) women age 18-65, (ii) for group A: women with histologically confirmed invasive breast cancer that is locally advanced (inflammatory and non-inflammatory LABC - any T3-T4 M0 and/or N2-3 M0 stages)
- women 18-65 with histologically confirmed high risk operable breast cancer (T2 and/or N+ M0 endocrine unresponsive breast cancers (ER- and PR-). and HER-2-/+, or any operable breast cancer with ≥ 4 involved axillary lymph nodes
- for group B (healthy controls): healthy women 18-65
Who cannot join
- (i) conditions that are associated with elevated serum levels of cytokines and other inflammatory markers (major inflammatory, chronic infectious or autoimmune systemic disease, cardiovascular disease, diabetes mellitus type I and II), or (ii) any concomitant or prior malignant disease. Those recruited for evaluation on cognitive functions will also be excluded for (iii) major pre-existing psychiatric history (including depression), dementia, alcohol abuse, or currently using a psychotropic medication that might lead to cognitive problems, (iv) insufficient English skills to comprehend the task instructions, and (v) impaired colour vision for reasons related to some of the test stimuli and tasks.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Inflammatory Markers in Predicting Disease Recurrency and Cognitive Performance in Women With High Risk and Locally Advanced Breast Cancer
Women with breast cancer undergo treatments that decrease the chance of recurrence of cancer, but are associated with several side effects, including declines in memory and attention and other thinking abilities. The causes of these declines are not known. However, we know that (i) people with cancer may have high levels of molecules in the blood (cytokines) that reflect inflammation; (ii) injection of cytokines into animals, and their use to treat some human diseases, can lead to decreased memory and attention; and (iii) in some advanced cancers cytokines predict disease outcome. This longitudinal study evaluates the relation of cytokines to decreased thinking abilities and to disease outcome over time. Results of this study may help develop interventions to prevent or minimize cognitive decline and identify women who are at high risk for recurrence, and such information could be used in treatment decisions and in the development of new treatment options.
Read the detailed description
SCIENTIFIC ABSTRACT Background: Women with locally advanced breast cancer (LABC), and women with high risk (T2-3/N+4, triple negative) yet operable breast cancer, undergo combined treatment including chemotherapy, surgery, irradiation, and hormonal treatment. These treatments decrease the chance of recurrence of cancer, but are associated with several side effects, including cognitive difficulties. About one third of breast cancer patients treated with chemotherapy report sustained decline in thinking abilities ('chemofog') after treatment. The causes for cognitive declines are not known. However there is recent information that: (i) people with cancer may have high levels of cytokines and other inflammatory molecules in the blood; (ii) injection of cytokines into animals, and their use to treat some human diseases, can lead to problems in memory and other cognitive abilities; (iii) some survivors of breast cancer have very high cytokine levels with no evidence that their cancer is still active and (iv) in some advanced cancers different cytokines and other inflammatory markers have prognostic information for disease outcome. Genetic polymorphisms of neuronal proteins (APOe, BDNF, COMT) are predictive for cognitive decline in non-cancer population). Objective: This longitudinal study will determine whether serum levels of cytokines and other inflammatory markers are related to 1) cognitive dysfunction; and 2) recurrence of disease in women with LABC/High Risk. Method: In 120 women with LABC/High risk relation of cytokines and inflammatory markers to cancer recurrence will be evaluated; blood will be drawn pre-chemotherapy, pre-surgery and then 1 and 2 years after diagnosis. In a subset of 60 women with LABC/high risk, cognitive performance will be evaluated at similar times as blood will be drawn. Similarly, a control group of 60 healthy women will be evaluated for cytokines and cognitive performance. We will also evaluate the predictive role of polymorphisms in genes encoding the neuronal proteins APOe, BDNF, and COMT for cognitive impairment. Data Analysis: The impact of cytokine levels and other inflammatory markers on cognitive performance over time will be evaluated using mixed model regression. Multivariate model will be applied to assess the impact of LABC/high risk and chemotherapy on cognitive functions. Cox proportional-hazard model will evaluate the relationship of cytokines and other blood markers on Time-To-Progression to identify variables that predict reoccurrence. Hypotheses: Cytokines and inflammatory markers are related to cognitive impairment and in disease outcome in women with locally advanced and high risk operable breast cancers. Genetic polymorphisms of neuronal proteins (APOe, BDNF, and COMT) are predictive for increased cognitive decline after diagnoses and treatment of these cancers. Implications: Increased knowledge about the causes of cognitive problems in women with breast cancer should allow development of strategies to prevent or minimize these unpleasant symptoms. Cytokines and other biomarkers might be predictive for disease outcome in women with breast cancer and used in tailoring of adjuvant treatment and as potential targets in development of new therapies.
- Conditions
- Locally Advanced Breast Cancer, Breast Cancer
- Keywords
- Breast, Neoplasm, Locally Advanced, Stage IV, Stage III, Cognitive Function, Cytokines, Inflammatory, Node positive
- Medical subject headings
- Breast Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Bloods Only (B) | Women aged 18-65 years with a newly diagnosed locally advanced or high risk operable breast cancer | |
| A-Cog | Women aged 18-65 years newly diagnosed with LABC/high risk who are willing and able to complete cognitive testing. | |
| Control (C) | Healthy women aged 18-65 years who are willing and able to complete cognitive testing. | |
| A1-Cog | Women newly diagnosed locally advanced or high risk breast cancer that qualify for cognitive testing but have a condition related to elevated serum levels of cytokines or other inflammatory markers. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive performance expressed by raw scores, T and Z scores
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2008 (estimated)
- Study startAug 2008
- Primary completionSep 2012
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Breast CancerStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lori Bernstein, PhD, Principal investigator, University Health Network, Princess Margaret HospitalBostjan Seruga, MD, Principal investigator, PMH UHN
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00756132
- Sponsor's protocol ID
- BernLCyto-Cog
- Acronym
- Cyto-Cog
- Status last verified
- Feb 2018
- First submitted
- 17 Sep 2008
- Last updated
- 28 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Inflammatory Markers in Predicting Disease Recurrency and Cognitive Performance in Women With High Risk and Locally Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00756132
- Acronym / sponsor ID
- Cyto-Cog / BernLCyto-Cog
- Conditions
- Locally Advanced Breast Cancer, Breast Cancer
- Keywords
- Breast, Neoplasm, Locally Advanced, Stage IV, Stage III, Cognitive Function, Cytokines, Inflammatory
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Sep 2012 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 19 Sep 2008 (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.
Women with breast cancer undergo treatments that decrease the chance of recurrence of cancer, but are associated with several side effects, including declines in memory and attention and other thinking abilities. The causes of these declines are not known. However, we know that (i) people with cancer may have high levels of molecules in the blood (cytokines) that reflect inflammation; (ii) injection of cytokines into animals, and their use to treat some human diseases, can lead to decreased memory and attention; and (iii) in some advanced cancers cytokines predict disease outcome. This longitudinal study evaluates the relation of cytokines to decreased thinking abilities and to disease outcome over time. Results of this study may help develop interventions to prevent or minimize cognitive decline and identify women who are at high risk for recurrence, and such information could be used in treatment decisions and in the development of new treatment options.
Detailed description
SCIENTIFIC ABSTRACT Background: Women with locally advanced breast cancer (LABC), and women with high risk (T2-3/N+4, triple negative) yet operable breast cancer, undergo combined treatment including chemotherapy, surgery, irradiation, and hormonal treatment. These treatments decrease the chance of recurrence of cancer, but are associated with several side effects, including cognitive difficulties. About one third of breast cancer patients treated with chemotherapy report sustained decline in thinking abilities ('chemofog') after treatment. The causes for cognitive declines are not known. However there is recent information that: (i) people with cancer may have high levels of cytokines and other inflammatory molecules in the blood; (ii) injection of cytokines into animals, and their use to treat some human diseases, can lead to problems in memory and other cognitive abilities; (iii) some survivors of breast cancer have very high cytokine levels with no evidence that their cancer is still active and (iv) in some advanced cancers different cytokines and other inflammatory markers have prognostic information for disease outcome. Genetic polymorphisms of neuronal proteins (APOe, BDNF, COMT) are predictive for cognitive decline in non-cancer population). Objective: This longitudinal study will determine whether serum levels of cytokines and other inflammatory markers are related to 1) cognitive dysfunction; and 2) recurrence of disease in women with LABC/High Risk. Method: In 120 women with LABC/High risk relation of cytokines and inflammatory markers to cancer recurrence will be evaluated; blood will be drawn pre-chemotherapy, pre-surgery and then 1 and 2 years after diagnosis. In a subset of 60 women with LABC/high risk, cognitive performance will be evaluated at similar times as blood will be drawn. Similarly, a control group of 60 healthy women will be evaluated for cytokines and cognitive performance. We will also evaluate the predictive role of polymorphisms in genes encoding the neuronal proteins APOe, BDNF, and COMT for cognitive impairment. Data Analysis: The impact of cytokine levels and other inflammatory markers on cognitive performance over time will be evaluated using mixed model regression. Multivariate model will be applied to assess the impact of LABC/high risk and chemotherapy on cognitive functions. Cox proportional-hazard model will evaluate the relationship of cytokines and other blood markers on Time-To-Progression to identify variables that predict reoccurrence. Hypotheses: Cytokines and inflammatory markers are related to cognitive impairment and in disease outcome in women with locally advanced and high risk operable breast cancers. Genetic polymorphisms of neuronal proteins (APOe, BDNF, and COMT) are predictive for increased cognitive decline after diagnoses and treatment of these cancers. Implications: Increased knowledge about the causes of cognitive problems in women with breast cancer should allow development of strategies to prevent or minimize these unpleasant symptoms. Cytokines and other biomarkers might be predictive for disease outcome in women with breast cancer and used in tailoring of adjuvant treatment and as potential targets in development of new therapies.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Bloods Only (B) | – | –Women aged 18-65 years with a newly diagnosed locally advanced or high risk operable breast cancer |
| A-Cog | – | –Women aged 18-65 years newly diagnosed with LABC/high risk who are willing and able to complete cognitive testing. |
| Control (C) | – | –Healthy women aged 18-65 years who are willing and able to complete cognitive testing. |
| A1-Cog | – | –Women newly diagnosed locally advanced or high risk breast cancer that qualify for cognitive testing but have a condition related to elevated serum levels of cytokines or other inflammatory markers. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Women ages 18-65 with a newly diagnosed locally advanced breast cancer and healthy women ages 18-65.
Key inclusion criteria (3 listed)
- (i) women age 18-65, (ii) for group A: women with histologically confirmed invasive breast cancer that is locally advanced (inflammatory and non-inflammatory LABC - any T3-T4 M0 and/or N2-3 M0 stages)
- women 18-65 with histologically confirmed high risk operable breast cancer (T2 and/or N+ M0 endocrine unresponsive breast cancers (ER- and PR-). and HER-2-/+, or any operable breast cancer with ≥ 4 involved axillary lymph nodes
- for group B (healthy controls): healthy women 18-65
Key exclusion criteria (1 listed)
- (i) conditions that are associated with elevated serum levels of cytokines and other inflammatory markers (major inflammatory, chronic infectious or autoimmune systemic disease, cardiovascular disease, diabetes mellitus type I and II), or (ii) any concomitant or prior malignant disease. Those recruited for evaluation on cognitive functions will also be excluded for (iii) major pre-existing psychiatric history (including depression), dementia, alcohol abuse, or currently using a psychotropic medication that might lead to cognitive problems, (iv) insufficient English skills to comprehend the task instructions, and (v) impaired colour vision for reasons related to some of the test stimuli and tasks.
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
Cognitive performance expressed by raw scores, T and Z scores
Time frame: 2 years
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 28 Feb 2018.
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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.
Lori Bernstein, PhD principal investigator
University Health Network, Princess Margaret Hospital
Bostjan Seruga, MD principal investigator
PMH UHN
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 Locally Advanced Breast Cancer and Breast Cancer, run by University Health Network, Toronto at 1 site in Canada.
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 3 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 28 Feb 2018. 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 Canada. 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?
Cognitive performance expressed by raw scores, T and Z scores (time frame: 2 years). 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 28 Feb 2018; AzTrials last refreshed its copy on 27 Oct 2026.