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Presurgical trial of metformin in overweight and obese patients with newly diagnosed breast cancer.

ABSTRACT: We conducted a presurgical trial to assess the tissue-related effects of metformin in overweight/obese breast cancer (BC) patients.Metformin 1,500 mg daily was administered to 35 nondiabetics with stage 0-III BC, body mass index (BMI) ? 25 kg/m(2). The primary endpoint was tumor proliferation change (i.e., ki-67). Tumor proliferation change was compared to untreated historical controls, matched by age, BMI, and stage.There was no reduction in ln(ki-67) after metformin (p = .98) or compared to controls (p = .47). There was a significant reduction in BMI, cholesterol, and leptin.Despite no proliferation changes, we observed reductions in other relevant biomarkers.

SUBMITTER: Kalinsky K

PROVIDER: S-EPMC4435671 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Presurgical trial of metformin in overweight and obese patients with newly diagnosed breast cancer.

Kalinsky Kevin K Crew Katherine D KD Refice Susan S Xiao Tong T Wang Antai A Feldman Sheldon M SM Taback Bret B Ahmad Aqeel A Cremers Serge S Hibshoosh Hanina H Maurer Matthew M Hershman Dawn L DL

Cancer investigation 20140307 4

<h4>Introduction</h4>We conducted a presurgical trial to assess the tissue-related effects of metformin in overweight/obese breast cancer (BC) patients.<h4>Methods</h4>Metformin 1,500 mg daily was administered to 35 nondiabetics with stage 0-III BC, body mass index (BMI) ≥ 25 kg/m(2). The primary endpoint was tumor proliferation change (i.e., ki-67). Tumor proliferation change was compared to untreated historical controls, matched by age, BMI, and stage.<h4>Results</h4>There was no reduction in ...[more]

PMID: 24605899

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Project description:BACKGROUND:Akkermansia muciniphila (AM) is a gram-negative, mucin-degrading bacteria inhabiting the gastrointestinal tract associated with host phenotypes and disease states. OBJECTIVE:Explore characteristics of overweight and obese female early-stage (0 to II) breast cancer patients with low AM relative abundance (LAM) vs high (HAM) enrolled in a presurgical weight-loss trial. DESIGN:Secondary analysis of pooled participants in a randomized controlled trial (NCT02224807). PARTICIPANTS/SETTING:During the period from 2014 to 2017, 32 female patients with breast cancer were randomized to weight-loss or attention-control arms from time of diagnosis-to-lumpectomy (mean=30±9 days). INTERVENTION:All were instructed to correct nutrient deficiencies via food sources and on upper-body exercises. The weight-loss group received additional guidance to promote 0.5 to 1 kg/wk weight-loss via energy restriction and aerobic exercise. MAIN OUTCOME MEASURES:At baseline and follow-up, sera, fecal samples, two-24 hour dietary recalls and dual x-ray absorptiometry were obtained. Bacterial DNA was isolated from feces and polymerase chain reaction (16S) amplified. Inflammatory cytokines were measured in sera. STATISTICAL ANALYSES PERFORMED:Differences between LAM and HAM participants were analyzed using t tests and nonparametric tests. Spearman correlations explored relationships between continuous variables. RESULTS:Participants were aged 61±9 years with body mass index 34.8±6. Mean AM relative abundance was 0.02% (0.007% to 0.06%) and 1.59% (0.59% to 13.57%) for LAM and HAM participants, respectively. At baseline, women with HAM vs LAM had lower fat mass (38.9±11.2 kg vs 46.4±9.0 kg; P=0.044). Alpha diversity (ie, species richness) was higher in women with HAM (360.8±84.8 vs 282.4±69.6; P=0.008) at baseline, but attenuated after weight-loss (P=0.058). At baseline, interleukin-6 level was associated with species richness (?=-0.471, P=0.008) and fat mass (?=0.529, P=0.002), but not AM. Change in total dietary fiber was positively associated with AM in LAM (?=0.626, P=0.002), but not HAM (?=0.436, P=0.180) participants. CONCLUSIONS:Among women with early-stage breast cancer, body composition is associated with AM, microbiota diversity, and interleukin-6 level. AM may mediate the effects of dietary fiber in improving microbiota composition.

Dataset Information

Presurgical trial of metformin in overweight and obese patients with newly diagnosed breast cancer.

Publications

Presurgical trial of metformin in overweight and obese patients with newly diagnosed breast cancer.

Similar Datasets

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