Effect of metformin vs placebo on and metabolic factors in NCIC CTG MA.32.
BACKGROUND
Metformin may improve metabolic factors (insulin, glucose, leptin, highly sensitive C-reactive protein [hs-CRP]) associated with poor breast cancer outcomes. The NCIC Clinical Trials Group (NCIC CTG) MA.32 investigates effects of metformin vs placebo on invasive disease-free survival and other outcomes in early breast cancer. Maintaining blinding of investigators to outcomes, we conducted a planned, Data Safety Monitoring Committee-approved, analysis of the effect of metformin vs placebo on weight and metabolic factors at six months, including examination of interactions with baseline body mass index (BMI) and insulin, in the first 492 patients with paired blood samples.


METHODS
Eligible nondiabetic subjects with T1-3, N0-3, M0 breast cancer who had completed surgery and (neo)adjuvant chemotherapy (if given) provided fasting plasma samples at random assignment and at six months. Glucose was measured locally; blood was aliquoted, frozen, and stored at -80°C. Paired plasma aliquots were analyzed for insulin, hs-CRP, and leptin. Spearman correlation coefficients were calculated and comparisons analyzed using Wilcoxon signed rank test. All statistical tests were two-sided.


RESULTS
Mean age was 52.1±9.5 years in the metformin group and 52.6 ± 9.8 years in the placebo group. Arms were balanced for estrogen/progesterone receptor, BMI, prior (neo)adjuvant chemotherapy, and stage. At six months, decreases in weight and blood variables were statistically significantly greater in the metformin arm (vs placebo) in univariate analyses: weight -3.0%, glucose -3.8%, insulin -11.1%, homeostasis model assessment -17.1%, leptin -20.2%, hs-CRP -6.7%; all P values were less than or equal to .03. There was no statistically significant interaction of change in these variables with baseline BMI or insulin.


CONCLUSIONS
Metformin statistically significantly improved weight, insulin, glucose, leptin, and CRP at six months. Effects did not vary by baseline BMI or fasting insulin.
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS). pgoodwin@mtsinai.on.ca.
Pamela J
PJ
Goodwin
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Wendy R
WR
Parulekar
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Karen A
KA
Gelmon
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Lois E
LE
Shepherd
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Jennifer A
JA
Ligibel
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Dawn L
DL
Hershman
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Priya
P
Rastogi
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Ingrid A
IA
Mayer
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Timothy J
TJ
Hobday
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Julie
J
Lemieux
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Alastair M
AM
Thompson
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Kathleen I
KI
Pritchard
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Timothy J
TJ
Whelan
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Som D
SD
Mukherjee
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Haji I
HI
Chalchal
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Conrad D
CD
Oja
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Katia S
KS
Tonkin
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Vanessa
V
Bernstein
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Bingshu E
BE
Chen
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada (PJG); NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada (WRP, LES, BEC); NCIC Clinical Trials Group, British Columbia Cancer Agency, University of British Columbia, Vancouver, British Columbia, Canada (KAG); Dana Farber Cancer Institute, Harvard Medical School, Boston, MA (JAL); Columbia University Medical Center, New York, NY (DLH); National Surgical Adjuvant Breast and Bowel Project, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA (PR); Vanderbilt-Ingram Medical Center, Vanderbilt University Medical Center, Nashville, TN (IAM); Mayo Clinic College of Medicine, Rochester, MN (TJH); Centre de recherche du CHU de Québec, Unité de recherche en santé des populations Hôpital du Saint-Sacrement, Quebec, Quebec, Canada (JL); National Cancer Research Institute Breast Clinical Studies Group, London, UK (AMT); Sunnybrook Odette Cancer Center, University of Toronto, Toronto, Ontario, Canada (KIP); Juravinski Cancer Center at Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada (TJW, SDM); Allan Blair Cancer Centre, Regina, Saskatchewan, Canada (HIC); British Columbia Cancer Agency, Fraser Valley Center, Surrey, British Columbia, Canada (CDO); University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada (KST); British Columbia Cancer Agency - Vancouver Island Center, University of British Columbia, British Columbia, Canada (VB); Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, University of Toronto, Toronto, Ontario, Canada (VS).
Vuk
V
Stambolic
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002097:C-Reactive Protein / Q000187:drug effects / Q000378:metabolism; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood*; D008687:Metformin / Q000494:pharmacology*; D008875:Middle Aged; D009367:Neoplasm Staging; D009656:North America / Q000453:epidemiology; D012107:Research Design; D018709:Statistics, Nonparametric; D013557:Switzerland / Q000453:epidemiology; D006113:United Kingdom / Q000453:epidemiology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D002097:C-Reactive Protein; D008687:Metformin