Evidence map›Paper›PMID 25253174›Full record

Trial reportBreast cancer research and treatment2014

Differential effects of metformin on breast cancer proliferation according to markers of insulin resistance and tumor subtype in a randomized presurgical trial.

Andrea DeCensi, Matteo Puntoni, Sara Gandini, Aliana Guerrieri-Gonzaga, Harriet Ann Johansson, Massimiliano Cazzaniga, Giancarlo Pruneri, Davide Serrano, Matthias Schwab, Ute Hofmann and 8 more

Open access · hybridAbstract readClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research and treatment, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

49 citing papers in PubMed, 76 citations in OpenAlex.

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  3. PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
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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

18 authors at 5 institutions in 3 countries.

Andrea DeCensiDivision of Medical Oncology, E.O. Ospedali Galliera, Mura Delle Cappuccine 14, 16128, Genoa, Italy, andrea.decensi@galliera.it.
Matteo Puntoni
Sara Gandini
Aliana Guerrieri-Gonzaga
Harriet Ann Johansson
Massimiliano Cazzaniga
Giancarlo Pruneri
Davide Serrano
Matthias Schwab
Ute Hofmann
Serena Mora
Valentina Aristarco
Debora Macis
Fabio Bassi
Alberto Luini
Matteo Lazzeroni
Bernardo Bonanni
Michael N Pollak
European Institute of Oncology · ITEnte Ospedaliero Ospedali Galliera · ITDr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · DEMcGill University · CAUniversity of Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment of diabetics with metformin is associated with decreased breast cancer risk in observational studies, but it remains unclear if this drug has clinical antineoplastic activity. In a recent presurgical trial, we found a heterogeneous effect of metformin on breast cancer proliferation (ki-67) depending upon insulin resistance (HOMA index). Here, we determined the associations of additional serum biomarkers of insulin resistance, tumor subtype, and drug concentration with ki-67 response to metformin. Two-hundred non-diabetic women were randomly allocated to metformin (850 mg/bid) or placebo for 4 weeks prior to breast cancer surgery. The ki-67 response to metformin was assessed comparing data obtained from baseline biopsy (ki-67 and tumor subtype) and serum markers (HOMA index, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, hs-CRP, adiponectin) with the same measurements at definitive surgery. For patients with a blood sample taken within 24 h from last drug intake, metformin level was measured. Compared with placebo, metformin significantly decreased ki-67 in women with HOMA > 2.8, those in the lowest IGFBP-1 quintile, those in the highest IGFBP-3 quartile, those with low free IGF-I, those in the top hs-CRP tertile, and those with HER2-positive tumors. In women with HOMA index > 2.8, drug levels were positively correlated with the ki-67 decrease, whereas no trend was noted in women with HOMA < 2.8 (p-interaction = 0.07). At conventional antidiabetic doses, the effect of metformin on tumor ki-67 of non-diabetic breast cancer patients varies with host and tumor characteristics. These findings are relevant to design breast cancer prevention and treatment trials with metformin.

Indexed as

Insulin ResistanceAdultBiomarkers, TumorBreast NeoplasmsCell ProliferationDouble-Blind MethodFemaleHumansHypoglycemic AgentsMetforminBiomarkers, TumorHypoglycemic AgentsMetformin

Identifiers

PMID25253174
PMCPMC4196136
OpenAlexW2151962431

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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 Socratic graph.