Dose–response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial

Kathryn H. Schmitz, Nancy I. Williams, Despina Kontos, Susan Domchek, Knashawn H. Morales, Wei Ting Hwang, Lorita L. Grant, Laura DiGiovanni, Domenick Salvatore, Desire’ Fenderson, Mitchell Schnall, Mary Lou Galantino, Jill Stopfer, Mindy S. Kurzer, Shandong Wu, Jessica Adelman, Justin C. Brown, Jerene Good

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Medical and surgical interventions for elevated breast cancer risk (e.g., BRCA1/2 mutation, family history) focus on reducing estrogen exposure. Women at elevated risk may be interested in less aggressive approaches to risk reduction. For example, exercise might reduce estrogen, yet has fewer serious side effects and less negative impact than surgery or hormonal medications. Randomized controlled trial. Increased risk defined by risk prediction models or BRCA mutation status. Eligibility: Age 18–50, eumenorrheic, non-smokers, and body mass index (BMI) between 21 and 50 kg/m2. 139 were randomized. Treadmill exercise: 150 or 300 min/week, five menstrual cycles. Control group maintained exercise <75 min/week. Primary outcome: Area under curve (AUC) for urinary estrogen. Secondary measures: urinary progesterone, quantitative digitized breast dynamic contrast-enhanced magnetic resonance imaging background parenchymal enhancement. Mean age 34 years, mean BMI 26.8 kg/m2. A linear dose–response relationship was observed such that every 100 min of exercise is associated with 3.6 % lower follicular phase estrogen AUC (linear trend test, p = 0.03). No changes in luteal phase estrogen or progesterone levels. There was also a dose–response effect noted: for every 100 min of exercise, there was a 9.7 % decrease in background parenchymal enhancement as measured by imaging (linear trend test, p = 0.009). Linear dose–response effect observed to reduce follicular phase estrogen exposure measured via urine and hormone sensitive breast tissue as measured by imaging. Future research should explore maintenance of effects and extent to which findings are repeatable in lower risk women. Given the high benefit to risk ratio, clinicians can inform young women at increased risk that exercise may blunt estrogen exposure while considering whether to try other preventive therapies.

Original languageEnglish (US)
Pages (from-to)309-318
Number of pages10
JournalBreast Cancer Research and Treatment
Issue number2
StatePublished - Nov 1 2015

Bibliographical note

Funding Information:
The authors wish to acknowledge the advocacy organizations that assisted with recruitment for this study, principally FORCE (Facing Our Risk of Cancer Empowered), the study participants, and the National Institutes of Health/National Cancer Institute for Grant R01-CA131333. The work of Kelsey Pears and Ellen Bingham is gratefully acknowledged. This work was also supported by discounts for treadmills from Smooth Fitness, Inc., King of Prussia, PA. The project described was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000003. Several study investigators were supported by the Basser Center at the University of Pennsylvania’s Abramson Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© 2015, Springer Science+Business Media New York.


  • Breast MRI
  • Breast cancer
  • Clinical trial
  • Estrogens
  • Exercise


Dive into the research topics of 'Dose–response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial'. Together they form a unique fingerprint.

Cite this