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Precision Prevention:Obesity and Breast Cancer
Clifford A. Hudis, MDChief, Breast Medicine Service, MSKCC
Professor of Medicine, WCMC
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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.
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Cancer Risk Factors
• Unmodifiable:– Gender– Age– Germline
• Modifiable:– Tobacco– Behavior– Exposures (toxins, viral, etc…)
Luther Terry, MD9th Surgeon General of the United States
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After Menopause: Increased BMI is Associated with Breast Cancer
Trentham-Dietz et al, Am J Epid 1997
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Obesity Worsens Cancer Outcomes (Female Below)
Calle EE, et al. N Engl J Med 2003.
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Source: Behavioral Risk Factor Surveillance System, CDC.
2000
Obesity Has Increased Among U.S. Adults….BRFSS, 1990, 2000, 2010
(*BMI 30, or about 30 lbs. overweight for 5’4” person)
2010
1990
No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%
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Accessed 26 May 2014 http://healthyamericans.org/report/100/
….And Is Projected To Worsen By 2030
>60% are Obese
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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
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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
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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?)
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Copyright © American Society of Clinical Oncology
Sinicrope, F. A. et al. J Clin Oncol; 29:4-7 2011
Multiple Pathways that appear to directly link obesity with breast cancer
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Is post-menopausal breast cancer a consequence of
inflammation? How?
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Preclinical Study To Investigate the Obesity InflammationAromatase axis
Female C57BL/6J Mice (n=40)
10 weeks of low fat (10kcal%) or
high fat (60kcal%) diet
4 weeks of age Ovariectomy (n=20)
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.
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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.
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Obesity Causes A ChronicMicroscopic Inflammatory State
Adapted from Olefsky & Glass. Annu. Rev. Physiol. 2010;72:219-246.
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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.
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CLS-B are Common in the Breasts of Overweight and Obese Women: Pilot Study
CD68 stainH&E stain
100
80
60
40
20
0
P=0.003
Normal Overweight Obese
% o
f c
ases
wit
h C
LS
-B
1/12
7/106/8
Morris et al, Cancer Prev Res July 2011 4; 1021 doi: 10.1158/1940-6207.CAPR-11-0110
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Opportunities:
-Effective/durable calorie restriction-Dietary content/nutriceuticals-Precision exercise training -Conventional targeted therapies
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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