The effects of metformin and weight loss on biomarkers associated with breast cancer outcomes

Ruth E. Patterson, Catherine R. Marinac, Dorothy D. Sears, Jacqueline Kerr, Sheri J. Hartman, Lisa Cadmus-Bertram, Adriana Villaseñor, Shirley W. Flatt, Suneeta Godbole, Hongying Li, Gail A. Laughlin, Jesica Oratowski-Coleman, Barbara A. Parker, Loki Natarajan

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 ¼ 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] ¼ -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI ¼ -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI ¼ -15.0% to -0.8%) for insulin, -10.0% (95% CI ¼ -18.5% to -1.5%) for estradiol, -9.5% (95% CI ¼ -15.2% to -3.8%) for testosterone, and 7.5% (95% CI ¼ 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 ¼ -19.6% to -5.3%) for insulin and 5.3% (95% CI ¼ 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.

Original languageEnglish (US)
Article numberdjy040
JournalJournal of the National Cancer Institute
Volume110
Issue number11
DOIs
StatePublished - 2018
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The effects of metformin and weight loss on biomarkers associated with breast cancer outcomes'. Together they form a unique fingerprint.

Cite this