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J Natl Cancer Inst. 2018 Nov 1;110(11):1239-1247. doi: 10.1093/jnci/djy040.

The Effects of Metformin and Weight Loss on Biomarkers Associated With Breast Cancer Outcomes.

Author information

1
Department of Family Medicine and Public Health, La Jolla, CA.
2
Moores UC San Diego Cancer Center, La Jolla, CA.
3
Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
5
Department of Medicine, La Jolla, CA.
6
Department of Kinesiology, University of Wisconsin, Madison, WI.
7
UC San Diego, La Jolla, CA.

Abstract

Background:

This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis.

Methods:

Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided.

Results:

A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, ≥80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG.

Conclusions:

As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality.

PMID:
29788487
PMCID:
PMC6235688
[Available on 2019-05-18]
DOI:
10.1093/jnci/djy040

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