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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 InflammationAromatase 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