Intermittent Fasting: How it Can Reduce the Risk of Breast Cancer R...

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Time Restricted Eating: Can it reduce the risk of
breast cancer or recurrence?
Nick Webster, Ph.D., M.A.
Senior Research C...

Obesity and cancer risk
Studies of circadian-synchronized feeding in
preclinical models of obesity-driven breast cancer
Is...

Take home message
When you eat matters as much as
what you eat

Obesity is a risk factor for several cancers
AACR Cancer
Progress Report
2020

Obesity (BMI >30) = 31.4%
Overweight (BMI 25-29.9) = 35.2%
Overweight or obese = 67%
Prevalence of Obesity Among U.S. Adul...

Obesity shows significant racial disparity
NHW Hispanics
African
Americans

Prevalence of Obesity Among Women in 2020
<24.7% 24.7-27.0% 27.1-31.5% 31.6-33.1% >33.2%

Rates of Breast Cancer in Women in US
109-124 124-129 129-135 135-145
Rate per 100,000

Prevalence of Obesity Worldwide

Prevalence of Overweight or Obese Worldwide

Global incidence of Breast Cancer

C. Kang, D. LeRoith, and E.J. Gallagher et al. Endocrinology, 159:3801–3812 (2018)
Potential mechanisms linking
obesity/di...

How do we treat obesity?
Current strategies
1. Dieting (caloric restriction)
2. Exercise
3. Bariatric surgery
4. Drugs tar...

Weight loss after the age of 50 reduces risk
of breast cancer
Teras L.R., et al., Sustained Weight Loss and Risk of Breast...

Changing diet alone does not work
Women’s Healthy Eating and Living (WHEL)
• 640 pre- and 2448 post-menopausal women (28% ...

Diet and exercise also does not work
Rubinstein et al., Br J Cancer (2021). https://doi.org/10.1038/s41416-021-01393-y
Ong...

Physical activity can improve some cancer-
related health outcomes
Significant evidence exists for a beneficial effect of ...

Bariatric surgery reduces cancer risk
Schauer D.N et al., Ann Surg 2019;260:95-101
All cancers Obesity-associated cancers

Effect on breast cancer risk
Fiegelson H.S. et al., Ann Surg 2020;272:1053-1059

How do we treat obesity?
Current strategies
1. Dieting (caloric restriction)
2. Exercise
3. Bariatric surgery
4. Drugs tar...

Types of Intermittent Fasting
Hoddy K.K. et al., Obesity 28(1):S29-S37 (2020)
Ramadan fasting is out-of-phase version of t...

Physiology follows circadian rhythms
Patterson RE et al. J Acad Nutr Diet (2015) 115(8):1203-12.

What synchronizes the clock?
Gill and Panda, Cell 22:789-798 (2015)
Panda, Science 354:1008-1015 (2016)
Humans eat for ~18...

Does disrupting the clock alter metabolism?

Frank A. J. L. Scheer et al. PNAS 2009;106:11:4453-4458
Forced circadian misalignment in humans
disrupts metabolism
aligne...

McHill A.W. et al., Am J Clin Nutr, 106(5), 1213–1219 (2017)
Eating earlier in the day results in lower body
fat
110 indiv...

Arble D.M., et al., Obesity, 17(11):2100-
2102 (2009)
Swarmy S., et al., Hormones and Behavior 105:177-
184 (2018)
Out of ...

Circadian disruption and disease with aging
Gabriele Sulli, Emily N.C. Manoogian, Pam R. Taub, Satchidananda Panda. Traini...

Time Restricted Feeding
Ad libitum Feeding
Circadian Rhythms
Reinforced
Metabolism Corrected?
Synchronizing eating to circ...

Time-restricted feeding improves
metabolism
Chung H. et al., Metabolism 65:1743-1754, 2016; Das M. et al., Nature Commun 1...

TRF can prevent weight regain after dieting
H – High-Fat Diet AL – 24h access to food
L – Low-Fat Diet TRF – Time-restrict...

TRF improves glucose metabolism
Overeat Low-Fat Diet Overeat
H – High-Fat Diet
L – Low-Fat Diet

Does this work in humans?

Sutton et al., Cell Metabolism 2018 27:1212-1221
Study of early TRF in 8 pre-diabetic men
5-week randomized,
cross-over de...

Ten-Hour Time-Restricted Eating in
Patients with Metabolic Syndrome
19 participants with pre-
diabetes on statin or anti-
...

Heathy Heroes study design
Pam Taub and Satchin Panda, BMJ Open 2021;11:e045537
150 Fire Fighters randomized to Mediterran...

Can circadian synchronization inhibit
obesity-induced cancer growth?
Ad libitum Feeding
Reduce
Tumor Growth
Time restricte...

Obesity accelerates breast cancer in mice
Chung H.Y., et al., Oncogene 34(27):3504-13 (2014)
High-fat diet and genetic
mod...

Study Design: Post-menopausal breast cancer
Postmenopausal Female Mouse Models
OVX mice 4-vinylcyclohexene diepoxide (VCD)...

TRF reduces obesity-driven breast tumor growth
OVX-Py230 VCD-Py230 OVX-E0771
OVX-PyMT
Das M. et al., Nature Commun 12:565,...

TRF reduces growth of existing tumor
Das M. et al., Nature Commun 12:565, 2021
TRF started after tumors were visible by ul...

Insulin drives tumor growth in obese mice
Increasing insulin levels with an insulin pump reverses the TRF effect
Decreasin...

Does prolonged nightly fasting reduce
cancer risk in humans?
2413 breast cancer survivors in the Women’s Healthy Eating an...

• Time-restricted feeding improves metabolism in obese mice
• TRF inhibits tumor growth in three mouse models of obesity-
...

Webster Lab
Manasi Das Deepak Kumar Emilie Gross
Consuelo Sauceda Tyler Mandt Alexis Oberg
Liping Zheng Heejun Jung Panyis...

Circadian rhythms are driven by transcription
Core clocks regulate biological processes in 24-h cycles
Bmal1
Asher and Sas...

Obesity alters circadian rhythms
Mammary
Fat Pad
Tumor

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