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Role of Inflammatory Markers in Predicting Disease Recurrency and Cognitive Performance in Women With High Risk and Locally Advanced Breast Cancer

18 Years
65 Years
Open (Enrolling)
Locally Advanced Breast Cancer, Breast Cancer

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Trial Information

Role of Inflammatory Markers in Predicting Disease Recurrency and Cognitive Performance in Women With High Risk and Locally Advanced Breast Cancer

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.

Inclusion Criteria:

- (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

Exclusion Criteria:

- (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.

Type of Study:


Study Design:

Observational Model: Case Control, Time Perspective: Prospective

Outcome Measure:

Cognitive performance expressed by raw scores, T and Z scores

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Lori Bernstein, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Health Network, Princess Margaret Hospital


Canada: Health Canada

Study ID:




Start Date:

August 2008

Completion Date:

September 2015

Related Keywords:

  • Locally Advanced Breast Cancer
  • Breast Cancer
  • Breast
  • Neoplasm
  • Locally Advanced
  • Stage IV
  • Stage III
  • Cognitive Function
  • Cytokines
  • Inflammatory
  • Node positive
  • Breast Neoplasms