1. Low Fat Center for Energy Balance Journal Club Shannon Armbruster MD Gynecologic Oncology October 15, 2015

2. Overview Background – Breast Cancer Facts – Diets and Breast Cancer Risk Paper Presentation – Design, Setting, Participants – Intervention – Results – Conclusion/Relevance

4. The Facts: In 2012: 224,147 women in the United States were diagnosed with breast cancer.*† In 2012, 41,150 women in the United States died from breast cancer.*† †Source: U.S. Cancer Statistics Working Group, CDC.

6. Recommendations:

8. What does the Mediterranean diet (MeDiet) have to do with it?

9. Methods : 605 patients (mostly men) with Cardiovascular disease (CVD) randomized to MeDiet or control Results : Reduction in Risk of cancer 61% in Experimental Group (12 v 2 cancers of all subtypes)

10. Methods : 121,700 women from Nurses’ Health Study followed from 1984-2002 Results : Greater adherence to the MeDiet resulted in lower risk of ER – breast cancer

11. Methods : 335,062 women followed in a cohort study for 11 years Results : Mediterranean diet (MeDiet) reduced breast cancer by 6% overall 7% reduction in post menopausal women ER/PR- tumors reduced by 20% in postmenopausal women Lack of association between MeDiet and breast cancer in premenopausal women

12. Methods : 33,731 women followed in a cohort study for 9 years Results : No significant association between MeDiet and breast cancer Premenopausal women: Non-significant trend of increasing compliance with MeDiet and lower risk of breast cancer No clear trends in post menopausal women

13. Methods : 49,258 women aged 30 to 49 years at recruitment, followed from 1991/1992 to 2008 Results : No significant association between MeDiet and breast cancer in this cohort

16. Purpose : Evaluate the incidence of breast cancer after implementation of 2 Mediterranean diet interventions (olive oil v. nuts) or a low-fat diet

17. Participants Framed with the PREDIMED (Prevencion con Dieta Mediterranea) trial Women 60-80 years of age – Diabetes Mellitus Type 2 – At least 3 major CVD risk factors – Smoking, hypertension, elevated low-density lipoprotein cholesterol level, low high-density lipoprotein cholesterol level, overweight /obesity, or family history of premature coronary heart disease

18. Randomization and Intervention 4282 Women MeDiet with EVOO N=1476 MeDiet with Nuts N=1285 Control Diet (Low-Fat) N=1391

19. Interventions MeDiet Groups: Sessions: – Baseline and quarterly assessment – Personalized Advice Incentives: – Given Extra Virgin Olive Oil or Nuts Control Group Yearly low-fat diet leaflets Sessions* Incentives: – Non-food items* * Protocol modification in Oct. 2006

20. Baseline Characteristics of Female PREDIMED Participants

22. Risk of Invasive Breast Cancer: Per Intervention Group

25. Results High consumption of EVOO needed to obtain significant protection Non-significant reduction with nuts

26. Strengths Randomized design Little residual confounding Blinding of medical info while assessing outcomes

27. Limitations Secondary analysis Small number of breast cancer cases identified No proof baseline mammograms were free of disease No confirmation that all women even received a mammogram Lack of diversity Reproductive factors are unknown for participants Changes due to diet or olive oil? For the first 3 years, the control group was less “intense”

28. Limitations: Low-Fat Diet High fat diets associated with a higher risk of breast cancer – WHI (Women’s Health Initiative): higher risk of breast cancer with higher total fat consumption There is a possibility that the low-fat group would have had better outcomes, if they truly followed a low-fat diet

29. Oleocanthal Oleocanthal: inhibition of tumor growth, proliferation, migration, and invasion of BC cells Oleuropein Oleuropein: increased apoptosis of cultured breast cancer cells Hydroxytyrosol Hydroxytyrosol: reduce intracellular reactive oxygen species and prevent oxidative DNA damage Lignans Lignans: seen in association with lower rates of post menopausal breast cancer

30. Low Fat

31. Comments/ Discussion Weight as a factor? Impact of Reproductive Factors – Breast feeding – When a patient had children Generalizability?