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Precision Prevention:
Obesity and Breast Cancer
Clifford A. Hudis, MD
Chief, Breast Medicine Service, MSKCC
Professor of Medicine, WCMC
Take Home Points
• Obesity is a risk factor for cancer.
• Obesity/overweight is a/w low grade
inflammation and elements of the metabolic
syndrome including insulin resistance.
• Some phenotypically normal BMI individuals
share this identifiable pathophysiology.
• There are multiple opportunities for clinical
intervention.
Cancer Risk Factors
• Unmodifiable:
– Gender
– Age
– Germline
• Modifiable:
– Tobacco
– Behavior
– Exposures (toxins, viral, etc…)
Luther
Terry, MD
9th Surgeon
General of
the United
States
After Menopause: Increased BMI is Associated
with Breast Cancer
Trentham-Dietz et al, Am J Epid 1997
Obesity Worsens Cancer Outcomes
(Female Below)
Calle EE, et al. N Engl J Med 2003.
Obesity Has Increased Among U.S. Adults….
BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2000
1990
2010
No Data
<10%
10%–14%
15%–19%
20%–24%
Source: Behavioral Risk Factor Surveillance System, CDC.
25%–29%
≥30%
….And Is Projected To Worsen By 2030
>60%areObese
Accessed 26 May 2014 http://healthyamericans.org/report/100/
http://www.npr.org/sections/health-shots/2015/09/23/442801737/obesity-maps-put-racial-differences-on-stark-display?utm_source=npr_newsletter&utm_medium=email&utm_content=20150925&utm_campaign=npr_email_a_friend&utm_term=storyshare
Global Obesity Rates Since 1980
Ng et al, Lancet Published Online May 29, 2014 http://dx.doi.org/10.1016/ S0140-6736(14)60460-8
This Is A New World
1. Unprecedented rates of obesity
(What are the scientific implications?)
2. Broad public health implications
3. Overall Hypothesis:
Energy balance is the critical first issue.
(and then diet content?)
Multiple Pathways that appear to directly link obesity with breast cancer
Sinicrope, F. A. et al. J Clin Oncol; 29:4-7 2011
Copyright © American Society of Clinical Oncology
Is post-menopausal breast
cancer a consequence of
inflammation? How?
Preclinical Study To Investigate the Obesity
InflammationAromatase axis
Female C57BL/6J Mice (n=40)
4 weeks of age Ovariectomy (n=20)
10 weeks of low fat (10kcal%) or
high fat (60kcal%) diet
Low Fat
n=10
Low Fat
Ovariectomy
n=10
High Fat
n=10
High Fat
Ovariectomy
n=10
Subbaramaiah et al Cancer Prev Res (Phila). 2011 Mar;4(3):329-46. doi: 10.1158/1940-6207.CAPR-10-0381.
Diet Induced Obesity Causes Inflammation in the
Mammary Gland and Visceral Fat
Subbaramaiah et al Cancer Prev Res (Phila). 2011 Mar;4(3):329-46. doi: 10.1158/1940-6207.CAPR-10-0381.
Obesity Causes A Chronic
Microscopic Inflammatory State
Adapted from Olefsky & Glass. Annu. Rev. Physiol. 2010;72:219-246.
Is This Also True In Women’s Breasts?
•Normal breast white adipose tissue was
obtained from 30 women who underwent
surgery.
•Routine H&E staining and CD68 IHC was
performed.
CLS-B are Common in the Breasts of Overweight and
Obese Women: Pilot Study
CD68 stain
H&E stain
% of cases with CLS-B
100 P=0.003
80
7/10
6/8
60
40
20
1/12
0
Normal
Overweight
Obese
Morris et al, Cancer Prev Res July 2011 4; 1021 doi: 10.1158/1940-6207.CAPR-11-0110
Opportunities:
-Effective/durable calorie restriction
-Dietary content/nutriceuticals
-Precision exercise training
-Conventional targeted therapies
ASCO Priorities to Address Obesity-Cancer Link:
1. Increase providers’ and patients’ knowledge about obesity and cancer
2. Develop evidence-based recommendations, tools and resources to help
oncology providers address obesity with their patients
3. Obesity and cancer research
4. Improve access to obesity treatment services for cancer patients/survivors