Audio and slides for this presentation are available on YouTube: http://youtu.be/f0c2vMxQtUo 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.

2. 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

3. We all know that obesity means weighing too
much, but how much too much?
Is this the same for every person?
What is obesity?

4. 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

5. 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

6. 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

7. By 2030, “leanest” states expected to have
obesity rates of 40-50%

8. What does obesity have to do with
breast and GYN cancers?

9. Obesity Is Associated with Higher Risk of
Developing Breast Cancer
Eliassen et al, JAMA 2006

10. 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

11. Obesity Is Associated with Higher Risk of
Developing Uterine Cancer
Chang et al, CEBP 2007

12. Many studies show heavier women more likely to
die of breast, uterine, ovarian, and other cancers

13. 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

14. 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

15. 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

16. Inactive women are also at higher risk of developing
breast cancer
More cancer in inactive More cancer in active

17. Women who exercise after breast cancer
diagnosis also have better survival
Exercise and risk of breast cancer-related death

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

19. 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

20. 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!

21. 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

22. 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

23. Dietary-Weight
Loss and
Physical
Activity
Irwin ML. Exerc. Sport Sci. Rev. 2006; 34(4): 182-93
Biologic pathways linking energy balance and cancer

24. 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

25. 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)

26. 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

27. 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

28. Ki-67 expression pre and post-exercise program
Baseline biopsy (44%) Post-intervention (16%)

29. 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

30. 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

31. Many thanks to Dr. Jennifer Ligibel for her
expertise and leadership

32. 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