Christina M. Dieli-Conwright, PhD, MPH Assistant Professor

1. Christina M. Dieli-Conwright, PhD, MPH Assistant Professor Metabolic Dysregulation and Exercise in Breast Cancer Survivors: Results from a RCT and Implications for WHI Collaboration

2. Metabolic Syndrome (MSY) Blood Pressure ≥ 130/85 or medication HDL < 40 mg/dL(men) < 50 mg/dL (women) Insulin Resistance Waist Circumference > 40 in (men) > 35 in (women) Glucose ≥ 100 mg/dL or medication Triglycerides ≥ 150 mg/dLor medication AHA/NHLBI

3. Chemotherapy may contribute to the onset of MSY. Changes in MSY After Chemotherapy Among Patients with Early-Stage Breast Cancer Dieli-Conwright et al., Cancer, 2015

4. MSY is linked to poor cancer outcomes. O’Flanagan et al., HormMol Bio ClinInvestig, 2015

5. Exercise targets biologic mechanisms related to cancer risk and cardiometabolic disease. Metabolic Syndrome1 Muscle Fat ↑ Muscle ↑ Glucose uptake ↓ Inflammation ↓ Fat ↓ Glucose uptake ↓ Inflammation Exercise Cancer2,3 1 Pedersen et al., Nat Rev Endocrinol, 2012 2 Wekesa et al., Prostate Cancer Prostatic Dis, 2015 3 McTiernan, Nat Rev Cancer, 2008

6. Exercise Recommendations for Cancer Survivors • Strength Training • At least 2 x/week • Moderate Exercise • 150 min/week • Vigorous Exercise • 75 min/week “Achieve and maintain a healthy weight” Rock et al. 2012, Ca Cancer J Clin, Schmitz et al. 2010, Med Sci Sports Exerc

7. Screening of all newly diagnosed breast cancer survivors scheduled for surgery/treatment at the USC NCCC or LAC Written informed consent Randomization Baseline assessments (within 0-6 months post-treatment) Primary Aim: To determine whether a 16-week exercise intervention will improve components of MetSin overweight/obese breast cancer survivors Progressive combined exercise training (PCT) Usual Care 16 weeks N = 50 16 weeks N = 50 Endpoint assessments Follow-up assessments (3 months post-intervention) Progressive combined exercise training (optional) Dieli-Conwright et al., BMC Cancer, 2014

8. Outcome MeasuresBaseline (Week 0) & Post-Testing (month 4), Follow-up (PCT only, month 7)

9. Exercise Intervention: PCT Progressive Combined Training Ligibel et al. JCO, 2008

10. Exercise Intervention

11. Consort Diagram

12. Baseline Participant Characteristics

13. Presence of MetS at baseline, four months, and seven months

14. Exercise Improves MSY in Obese Postmenopausal Breast Cancer Survivors.

15. Exercise Improves Sarcopenic Obesity in Obese Postmenopausal Breast Cancer Survivors.

16. Metabolic Syndrome Body Composition Future Directions Exercise ↑ Skeletal muscle ↓ Adipose tissue Improved Prognosis ↑DFS ↓ Cell survival, proliferation, metastases

17. WHI: MetS, Exercise, and Breast Cancer Metabolic Syndrome Intervention: Home-, phone-, mHealth-based Physical Activity Observational Cancer Incidence & Mortality

18. Adipose Tissue Collaborators: Steve Mittelman, MD, PhD Jean Parmentier, PhD Fred Sattler, MD Wendy Mack, PhD K07 Mentors: Leslie Bernstein, PhD Tom Buchanan, MD Kerry Courneya, PhD Wendy Demark-Wahnefried, PhD Joanne Mortimer, MD DebuTripathy, MD Thank you!Acknowledgements Dedicated, motivated, energetic participants! USC Breast Oncology Collaborators: Darcy Spicer, MD Christy Russell, MD Jorge Nieva, MD Janice Lu, MD USC- Dieli Lab: KyuwanLee, MS Nathalie Sami, BS Breanna Orozco, BS DPT Students Funding: NCI K07CA160718 NCATS UL1TR001855