Using Bio Markers to Predict Disease Recurrence and Cognitive Function in High Risk Breast Ca
Condition: Locally Advanced Breast Cancer; Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

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. 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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Women ages 18-65 with a newly diagnosed locally advanced breast cancer and healthy women
        ages 18-65.
      
Keywords: Breast; Neoplasm; Locally Advanced; Stage IV; Stage III; Cognitive Function; Cytokines; Inflammatory; Node positive