Evidence map›Paper›PMID 28447237›Full record

Trial reportBreast cancer research and treatment2017

Effects of metformin versus placebo on vitamin B12 metabolism in non-diabetic breast cancer patients in CCTG MA.32.

Ana Elisa Lohmann, Mira F Liebman, William Brien, Wendy R Parulekar, Karen A Gelmon, Lois E Shepherd, Jennifer A Ligibel, Dawn L Hershman, Priya Rastogi, Ingrid A Mayer and 12 more

Open access · greenAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.7field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Relationship between metformin use and vitamin BJournal of diabetes investigation · 2020
    Article
  6. Review
  7. Metformin and Breast Cancer: Molecular Targets.Journal of mammary gland biology and neoplasia · 2019
    Review
  8. Pleiotropic Effects of Metformin on Cancer.International journal of molecular sciences · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 11 institutions in 2 countries.

Ana Elisa LohmannDepartment of Medicine, Division of Medical Oncology and Hematology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, 1284-600 University Ave, Toronto, ON, M5G 1X5, Canada.
Mira F LiebmanChildren's Hospital of Eastern Ontario, Ottawa, ON, Canada.
William BrienUniversity Health Network, University of Toronto, Toronto, ON, Canada.
Wendy R ParulekarCanadian Cancer Trials Group (CCTG), Cancer Research Institute, Queen's University, Kingston, ON, Canada.
Karen A GelmonBritish Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
Lois E ShepherdCanadian Cancer Trials Group (CCTG), Cancer Research Institute, Queen's University, Kingston, ON, Canada.
Jennifer A LigibelDana-Farber Cancer Institute, Boston, MA, USA.
Dawn L HershmanColumbia University Medical Center, New York, NY, USA.
Priya RastogiNational Surgical Adjuvant Breast and Bowel Project and University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Ingrid A MayerVanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
Timothy J HobdayMayo Clinic College of Medicine, Rochester, MN, USA.
Julie LemieuxCentre Hospitalier Universitaire de Québec, Quebec, QC, Canada.
Alastair Mark ThompsonDepartment of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Kathleen I PritchardSunnybrook Odette Cancer Centre and the University of Toronto, Toronto, ON, Canada.
Timothy Joseph WhelanJuravinski Cancer Centre, Hamilton, ON, Canada.
Som D MukherjeeJuravinski Cancer Centre, Hamilton, ON, Canada.
Haji I ChalchalAllan Blair Cancer Center, Regina, SK, Canada.
Vanessa BernsteinBritish Columbia Cancer Agency, Vancouver Island Center, University of British Columbia, Vancouver, BC, Canada.
Vuk StambolicPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
Bingshu E ChenCanadian Cancer Trials Group (CCTG), Cancer Research Institute, Queen's University, Kingston, ON, Canada.
Pamela Jean GoodwinDepartment of Medicine, Division of Medical Oncology and Hematology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, 1284-600 University Ave, Toronto, ON, M5G 1X5, Canada. pamela.goodwin@sinaihealthsystem.ca.
From the CCTG, Alliance, SWOG, ECOG, NSABP Cooperative Groups
BC Cancer Agency · CAMount Sinai Hospital · CAUniversity Health Network · CAColumbia University Irving Medical Center · USJuravinski Cancer Centre · CAMayo Clinic · USSunnybrook Health Science Centre · CAQueen's University · CAThe University of Texas MD Anderson Cancer Center · USUniversity of Toronto · CAVanderbilt University · US

Funding

NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8M
NCIC Clinical Trials Group - Canadian Collaborating Clinical Trials NetworkU10CA180863 · NCI · QUEEN'S UNIVERSITY AT KINGSTON · PI Janet Ellen Dancey · 2014 to 2026
$40.4M
Cancer Research UK 13953NCI NIH HHS U10 CA180863NCI NIH HHS U10 CA180868
6 · The paper itself

Abstract

backgroundMetformin is associated with low levels of vitamin B12 (VitB12) in patients with diabetes. The CCTG/MA.32 trial investigates the effects of metformin vs placebo on breast cancer (BC) outcomes in non-diabetic high-risk BC patients. We analyzed VitB12 at baseline and after 6 months of metformin (versus placebo) in the first 492 patients with paired blood samples.

methodsVitB12 was analyzed centrally in baseline and 6-month fasting plasma. Levels <181 pmol/L were considered deficient, 181-221 pmol/L borderline, and ≥222 pmol/L sufficient. Methylmalonic acid (MMA) and homocysteine (HC) were assayed in those with VitB12 levels <222 pmol/L. Statistical analyses used Spearman's rank correlation coefficients and Wilcoxon signed-rank test for continuous variables and Chi-square test for categorical variables.

results237 patients received metformin and 255 received placebo; median (inter quartile range) baseline VitB12 levels were 390 (290, 552) and 370 (290, 552) pmol/L in the metformin and placebo arms, respectively (p = 0.97). At 6 months, the median levels were 320 (244, 419) in the metformin versus 380 (286, 546) pmol/L in the placebo arm (p = 0.0001). At baseline, 15 patients (11 metformin and 4 placebo) had VitB12 <181 pmol/L, and at 6 months, 18 patients (15 metformin and 3 placebo) (p = 0.004). Median hemoglobin was similar at baseline, metformin, 130 g/L (124-137), and placebo arms, 131 g/L (124-137) (p = 0.38), and at 6 months, metformin, 131 g/L (91-162), and 131 g/L (106-169) in placebo group (p = 0.11). Of the 74 subjects with vitamin B12 <222 pmol/L at either time point (45 metformin, 29 placebo), at baseline MMA was normal in all patients and two had elevated HC (>15μmol/L). At 6 months, one patient (metformin) had MMA >0.4μmol/L and 3 (2 metformin, 1 placebo) had HC > 15μmol/L.

conclusionsThere was an increased rate of biochemical VitB12 deficiency after 6 months of metformin; this was not associated with anemia. Further research will investigate VitB12 levels in all subjects at baseline and at 6 and 60 months.

Indexed as

AdultAntineoplastic AgentsBreast NeoplasmsFemaleHomocysteineHumansMetforminMethylmalonic AcidMiddle AgedTreatment OutcomeVitamin B 12Antineoplastic AgentsHomocysteineMetforminMethylmalonic AcidVitamin B 12AnemiaBreast cancerHomocysteineMegaloblastic anemiaMetforminMethylmalonic acidVitamin B12

Identifiers

PMID28447237
PMCPMC5798974
OpenAlexW2608642020

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.