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A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density

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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Obesity is a known risk factor for post-menopausal breast cancer and may increase risk for triple negative breast cancer in premenopausal women. Intervention strategies are clearly needed to reduce obesity-associated breast cancer risk.

Methods

We conducted a Phase II double-blind, randomized, placebo-controlled trial of metformin in overweight/obese premenopausal women with components of metabolic syndrome to assess the potential of metformin for primary breast cancer prevention. Eligible participants were randomized to receive metformin (850 mg BID, n = 76) or placebo (n = 75) for 12 months. Outcomes included breast density, assessed by fat/water MRI with change in percent breast density as the primary endpoint, anthropometric measures, and intervention feasibility.

Results

Seventy-six percent in the metformin arm and 83% in the placebo arm (p = 0.182) completed the 12-month intervention. Adherence to study agent was high with more than 80% of participants taking ≥ 80% assigned pills. The most common adverse events reported in the metformin arm were gastrointestinal in nature and subsided over time. Compared to placebo, metformin intervention led to a significant reduction in waist circumference (p < 0.001) and waist-to-hip ratio (p = 0.019). Compared to placebo, metformin did not change percent breast density and dense breast volume but led to a numerical but not significant decrease in non-dense breast volume (p = 0.070).

Conclusion

We conclude that metformin intervention resulted in favorable changes in anthropometric measures of adiposity and a borderline decrease in non-dense breast volume in women with metabolic dysregulation. More research is needed to understand the impact of metformin on breast cancer risk reduction.

Trial registration

ClinicalTrials.gov NCT02028221. Registered January 7, 2014, https://clinicaltrials.gov/ct2/show/NCT02028221

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

T2DM:

Type 2 diabetes

AMPK:

AMP-activated protein kinase

ER:

Estrogen receptor

CBC/w diff:

Complete blood count with differential

CMP:

Comprehensive metabolic panel

AFFQ:

Arizona Food Frequency Questionnaire

AAFQ:

Arizona Activity Frequency Questionnaire

AE:

Adverse event

CTCAE:

Common Terminology Criteria for Adverse Events

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Acknowledgements

This work was supported by R01 CA172444 and P30 CA023074 from the National Cancer Institute. The authors wish to acknowledge Amy Carrier, Laura Duckett, Valerie Butler, Bonita Weible, Jerilyn San Jose, Catherine Cordova, Wade Chew, Heidi Fritz, Angela Yung, Roxanne Vann, and Shawndeena George for their contributions to the performance of the clinical study and endpoint analyses. The authors also would like to acknowledge the providers at the Gynecology Clinic at Banner-University Medical Center in Tucson for assistance in participant recruitment.

Funding

This work was supported by R01 CA172444 and P30 CA023074 from the National Cancer Institute.

Author information

Authors and Affiliations

  1. University of Arizona Cancer Center, University of Arizona, 1515 N Campbell Ave, Tucson, AZ, 85724, USA

    Edgar Tapia, Pavani Chalasani, Sara Centuori, Denise J. Roe, Jose Guillen-Rodriguez, Jean-Phillippe Galons, Cynthia A. Thomson, Maria Altbach, Jesse Trujillo, Liane Pinto, Jessica A. Martinez, Amit M. Algotar & H-H. Sherry Chow

  2. Department of Biological-Chemistry Sciences, University of Sonora, Hermosillo, Sonora, Mexico

    Diana Evelyn Villa-Guillen

  3. Department of Medicine, University of Arizona, Tucson, AZ, USA

    Pavani Chalasani, Sara Centuori & H-H. Sherry Chow

  4. Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ, USA

    Denise J. Roe

  5. Department of Radiology, Stony Brook University, Stony Brook, NY, USA

    Chuan Huang

  6. Department of Medical Imaging, University of Arizona, Tucson, AZ, USA

    Jean-Phillippe Galons & Maria Altbach

  7. Department of Health Promotion Sciences, University of Arizona, Tucson, AZ, USA

    Cynthia A. Thomson

  8. Department of Nutritional Sciences, University of Arizona, Tucson, AZ, USA

    Jessica A. Martinez

  9. Department of Family and Community Medicine, University of Arizona, Tucson, AZ, USA

    Amit M. Algotar

Authors
  1. Edgar Tapia
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  2. Diana Evelyn Villa-Guillen
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  4. Sara Centuori
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  6. Jose Guillen-Rodriguez
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  7. Chuan Huang
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  8. Jean-Phillippe Galons
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  9. Cynthia A. Thomson
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  10. Maria Altbach
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  11. Jesse Trujillo
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  12. Liane Pinto
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  13. Jessica A. Martinez
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  14. Amit M. Algotar
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  15. H-H. Sherry Chow
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Contributions

ET contributed to data acquisition, data analysis, data interpretation, and manuscript preparation, DVG contributed to data acquisition, data analysis, data interpretation, PC contributed to clinical evaluation, data acquisition, data analysis, data interpretation, SC contributed to data analysis, data interpretation, and manuscript revision, DR contributed to the study design, data analysis, data interpretation, and manuscript revision, JG-R contributed to data management and data analysis, CH contributed to fat/water MRI analysis, data interpretation, and manuscript revision, J-PG contributed to data acquisition, data interpretation, and manuscript revision, CT contributed to data interpretation and manuscript revision, MA contributed to the study design, data interpretation, and manuscript revision, JT contributed to data analysis and manuscript revision, LP contributed to data analysis and data interpretation, JM contributed to data interpretation and manuscript revision, MJ contributed to data interpretation and manuscript revision, H-HC contributed to the study design, clinical evaluation, data analysis, data interpretation, and manuscript preparation. All authors read and approved the final manuscript.

Corresponding author

Correspondence to H-H. Sherry Chow.

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Conflict of interest

The authors declare that they have no competing interests.

Ethical approval

The study was approved by the Institutional Review Board at The University of Arizona.

Consent to participate

Written informed consent was obtained from all participants.

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Not applicable.

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Tapia, E., Villa-Guillen, D.E., Chalasani, P. et al. A randomized controlled trial of metformin in women with components of metabolic syndrome: intervention feasibility and effects on adiposity and breast density. Breast Cancer Res Treat 190, 69–78 (2021). https://doi.org/10.1007/s10549-021-06355-9

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  • DOI: https://doi.org/10.1007/s10549-021-06355-9

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