Precision Prevention:Obesity and Breast Cancer

Clifford A. Hudis, MDChief, 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, MD9th 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.

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%

Accessed 26 May 2014 http://healthyamericans.org/report/100/

….And Is Projected To Worsen By 2030

>60% are Obese

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?)

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

Is post-menopausal breast cancer a consequence of

inflammation? How?

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.

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 ChronicMicroscopic 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 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

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