Trial Information

Biobehavioral Mechanisms of Fatigue in Patients Treated on NCIC CTG MA.32: A Phase III Randomized Trial of Metformin Versus Placebo on Recurrence and Survival in Early Stage Breast Cancer

OBJECTIVES:

- To prepare, separate into components, and store the blood specimens at the NSABP Serum
Bank at Baylor College of Medicine Breast Center for future DNA, RNA, and plasma
analysis, and to analyze specific proinflammatory cytokines, genetic polymorphisms, and
RNA expression arrays in collaborating laboratories at University of California, Los
Angeles (UCLA).

- To examine the association between markers of inflammation and symptoms of fatigue
among patients with and without exposure to metformin hydrochloride.

- To examine the relationship between single nucleotide polymorphism (SNPs) in the
promoter regions of IL-1 and IL-6 and symptoms of fatigue with and without exposure to
metformin hydrochloride.

- To examine RNA expression profiles in relationship to fatigue and compare the pattern
of expression in patients with and without exposure to metformin hydrochloride.

- To determine the biological and behavioral predictors of fatigue in breast cancer
patients in the five years post-randomization.

- To determine whether metformin is associated with reductions in inflammatory markers
and corresponding decreases in fatigue. (Exploratory)

OUTLINE: This is a multicenter study.

Patients' serum and plasma, collected at baseline and at 6, 12, and 24 months after NCIC CTG
MA.32 randomization, are analyzed for inflammatory markers, DNA polymorphisms, and RNA
expression arrays by ELISA, TaqMan PCR, and RT-PCR.

Patients complete the Fatigue Symptom Inventory (symptoms associated with fatigue, sleep
disturbance, depression, and endocrine therapy) at baseline and periodically during study.