Weight, Exercise and Cancer Risk

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Nancy Lin, MD, a breast oncologist in the Susan F. Smith Center for Women's Cancers at Dana-Farber, shares new data and research studies linking a healthy lifestyle to better treatment outcomes.

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  • Non obese = BMI less than 30; active is more than 1 hour/week of moderate to vigorous physical activity
  • Phase III randomized trial of first-line trastuzumab and paclitaxel  carboplatin (TPC) for MBC that was HER2+ IHC 2+ or 3+ (N=188)
    Rationale
    Preclinical synergy of trastuzumab and platinum agents
    In the pivotal CT  trastuzumab trial (H0648g), superior efficacy with the addition of trastuzumab
    Trial design1
    CT was administered on a q3w schedule, trastuzumab qw.
    Paclitaxel 175 mg/m2; carboplatin AUC 6
    CT was given for at least 6 cycles, with treatment beyond that as clinically indicated and at the investigators’ discretion.
    Trastuzumab was administered at the standard weekly dose (4 mg/kg week 1, then 2 mg/kg qw thereafter) until PD.
    Patients: all taxane-naive
    End points – primary: ORR; secondary: DOR, TTP, survival, and safety
  • $7 mil just for intervention, also require infrastructure and regulatory costs
  • Weight, Exercise and Cancer Risk

    1. 1. Weight, Physical Activity, and Cancer Risk and Outcomes Nancy Lin, MD Breast Oncology Program Susan F. Smith Center for Women’s Cancers at Dana-Farber April 10, 2014
    2. 2. We all know that obesity means weighing too much, but how much too much? Is this the same for every person? What is obesity?
    3. 3. Body Mass Index • Calculated according to the formula: kilograms/(meters)2 • Allows for creation of weight categories: • Underweight: BMI <18.5 kg/m2 • Normal weight: BMI 18.5-24.9 kg/m2 • Overweight: BMI 25-29.9 kg/m2 • Obese: BMI ≥30 kg/m2 » Class 1 obesity: 30-35 » Class 2 obesity: 35-40 » Class 3 obesity: >40
    4. 4. So what does this mean for an actual person? For a 5’4” woman: Normal weight: 110-144 Overweight: 145-173 Obese: 174+ Obesity is 30+ pounds of excess weight for 5’4” woman
    5. 5. Obesity has become dramatically more common in US over last 25 years Trends in Obesity Prevalence (%), Adults 18 and Older, US, 1985- 2010 http://www.cdc.gov/obesity/data/trends.html
    6. 6. By 2030, “leanest” states expected to have obesity rates of 40-50%
    7. 7. What does obesity have to do with breast and GYN cancers?
    8. 8. Obesity Is Associated with Higher Risk of Developing Breast Cancer Eliassen et al, JAMA 2006
    9. 9. Obesity Is Associated with Higher Risk of Developing Breast Cancer Eliassen et al, JAMA 2006 In this study, it is estimated that: •15% of breast cancer related to weight gain >2 kg since age 18 •4.4% of breast cancers related to weight gain >2 kg since menopause
    10. 10. Obesity Is Associated with Higher Risk of Developing Uterine Cancer Chang et al, CEBP 2007
    11. 11. Many studies show heavier women more likely to die of breast, uterine, ovarian, and other cancers
    12. 12. Example of a study looking at weight and breast cancer recurrence • Enrolled 2005 patients between 1997 and 1999 • All patients treated with modern chemotherapy • All patients received appropriate treatment regardless of weight CALGB 9741
    13. 13. Results: Leaner women had lower risk of breast cancer recurrence • Each 1 unit increase in BMI linked to a 1.5% increase in risk of breast cancer recurrence (and in risk of death) • For example, compared to a normal weight woman: • An overweight woman had an 8% increase in risk of recurrence • An obese woman had a 17% increase in risk of recurrence
    14. 14. Obesity is part of “Energy Balance”: Energy we take in Energy we “spend” What remains (Food) (Exercise + Metabolism) (Weight) _ = Each of these factors has been linked to cancer
    15. 15. Inactive women are also at higher risk of developing breast cancer More cancer in inactive More cancer in active
    16. 16. Women who exercise after breast cancer diagnosis also have better survival Exercise and risk of breast cancer-related death
    17. 17. Women who exercised had lower risk of cancer recurrence 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Recurrence * < 1 hour 1-3 hours 3-5 hours > 5 hours MET-Hrs/week *p=0.05, # p<0.004
    18. 18. Women who exercised had lower risk of cancer recurrence 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 Recurrence * < 1 hour 1-3 hours 3-5 hours > 5 hours MET-Hrs/week *p=0.05, # p<0.004 50% FEWER CANCER RECURRENCES IN WOMEN WHO EXERCISED > 3 HOURS/WEEK
    19. 19. What kind of exercise were these women doing? • The most common exercise was walking at a moderate pace • Benefits seen with walking at a 3-mile-per-hour pace for half an hour per day • Not necessary to run a marathon!
    20. 20. Similar Data in Endometrial Cancer Arem et al, JNCI 2013 Non obese = BMI less than 30 kg/m2; active = more than 1 hour/week of moderate to vigorous physical activity
    21. 21. How could obesity and physical activity affect cancer risk? • Short answer: no one is completely sure • Many potential factors could serve as links between obesity and breast cancer: • Insulin and other metabolic hormones • Inflammation • Estrogen and other sex hormones
    22. 22. Dietary-Weight Loss and Physical Activity Irwin ML. Exerc. Sport Sci. Rev. 2006; 34(4): 182-93 Biologic pathways linking energy balance and cancer
    23. 23. Exercise Insulin Study in Breast Cancer Survivors • Enrolled 101 inactive, overweight breast cancer survivors • Goal: to lower insulin levels through exercise • Exercise regimen: – Strength training – Cardio at home
    24. 24. How much exercise did women do? 0 20 40 60 80 100 120 140 Leg Calf Hamstr Quad Baseline Week 16 Strength: Aerobic Activity: Increase of 100 minutes/week (11 vs 110)
    25. 25. Results: Exercise lowered insulin by 28% -30 -25 -20 -15 -10 -5 0 5 Insulin Weight % Fat Hip Cir Waist Cir Exercise Control % Change over 16 weeks
    26. 26. SurgeryBaseline Biopsy 50 breast cancer patients Eligibility: • Newly diagnosed • Stage I-III • Plan to undergo definitive surgery Mind Body Intervention Exercise Intervention On-going work will study direct impact of exercise on breast tumors
    27. 27. Ki-67 expression pre and post-exercise program Baseline biopsy (44%) Post-intervention (16%)
    28. 28. 3675 women with early stage breast cancer: -Stage II-III -Within 12 months of diagnosis Health Education Intervention + 2-year Telephone-based Weight loss intervention Health Education Intervention Primary Outcome: Invasive disease free survival Secondary Outcomes: Overall survival, weight loss, change in diet and exercise patterns Alliance Trial of the Impact of Weight Loss on Outcomes in Early Breast Cancer
    29. 29. Conclusions • Obesity is increasingly common in the United States and beyond • Diet, physical activity and weight are all part of “energy balance”— and may influence cancer risk and outcomes • Research is needed: – to determine whether losing weight improves survival – to determine which patients most likely to benefit from weight control, exercise programs, or other lifestyle interventions
    30. 30. Many thanks to Dr. Jennifer Ligibel for her expertise and leadership
    31. 31. Acknowledgements • All the patients who have volunteered for our studies! • Team at DFCI • Jennifer Ligibel • Laura Shockro • Nancy Campbell • Anita Giobbie-Hurder & Bill Barry • Casey Peira • Liz Frank • Deborah Dillion • Eric Winer • Ann Partridge • Jeff Meyerhardt • Collaborators • Melinda Irwin (Yale) • Pam Goodwin (Univ of Toronto) • Anne McTiernan (FHCRC) • Lee Jones (Duke) • Funding: • Susan G Komen Foundation/Society for Women’s Health Research • NIH and NCI TREC • LIVESTRONG Foundation • CALGB • ASCO • Spivak and McMackin Foundations

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