1. Soy & Breast Cancer
Alyssa Moore
NUTR 700

2. Overview Breast Cancer Statistics & Risk Factors
The Role of Estrogen in the Body & specifically the breast
Phytoestrogens & Isoflavones in Soy
The Soy Controversey
Pros and Cons of Soy
Studies comparing Asian and Western populations
Pre-menopausal vs. Post-menopausal women & Tamoxifen Use
Soy Processing

3. The Facts
Breast cancer took the lives of 40,000 women last year in the United States
Estimated to be 231,840 new cases of invasive breast cancer in 2015 and 40,290 deaths in women
BRCA1 and BRCA2 mutations account for only 5-10% of breast cancers diagnosed in the US
Age & being female most common risk factors for breast cancer
2/3 of cases are in women 55 years and older
Age
Risk of Developing Breast Cancer 20
1 in 1,681 30
1 in 232 40
1 in 69 50
1 in 42 60
1 in 29 70
1 in 27
Lifetime Risk (up to age 85)
1 in 8

4. Other Risk Factors Family history High breast density on a mammogram
Exposure to large amounts of radiation at a young age
Never having children or having your first child after age 35
Younger age at first period (before age 12)
Older age at menopause (over age 55)
Alcohol use
Birth control use
Menopausal hormone therapy of estrogen plus progestin (continuous combined)
Overweight/obesity
Lack of exercise
Not breastfeeding

5. Role of Estrogen in the Female Body

6. Prolonged exposure to estrogen Increased cell proliferation
Increased risk of breast cancer

7. Phytoestrogens Phytoestrogens Coumestrans Isoflavanoids Lignans
Estrogen-like compounds occuring naturally in certain plant foods
Phytoestrogens-can have anti-estrogenic properties or estrogen-like properties
Split peas, long beans, alfalfa & clover sprouts
Legumes w/ soybeans as major dietary source
High fiber foods such as cereal brans & flaxseeds

8. Isoflavones in Soy
Soybean comprised of 50% genistein, 40% daidzein & 10% glycetin
Binds to both ER-alpha and ER-beta receptors
Higher affinity for ER-beta
ER-alpha: Increases cell proliferation in breast
ER-beta: Suppresses cell proliferation in breast
Antioxidant & anti-inflammatory properties
Daidzen & genistein most studied  genistein has most effects
Genistein=main isoflavone in soy that has shown effects (posiitve & negative)
Structure very simlar to that of estrogen, thus can occupy receptor
Only soybeans are primary source of genistein in human diet

9. What is the soy controversey?
Epidemiological studies-shown soy consumption is inversely associated w/ breast cancer risk
Genistein-conflicting studies but some show that it enhances proliferation of breast cancer cells in vitro & promotes estrogen dependent mammary growth in overiectomixed rats (studies have also shown that rats do not metabolize estrogen in same way)

10. Pros & Cons of Soy
Epidemiological studies show soy consumption is inversely associated w/ breast cancer risk
Soy constituents shown to have anti-cancer properties
May lower risk of osteoporosis, heart disease, breast cancer, & menopausal symptoms
In vitro, genistein can inhibit proliferation of ER(+) & ER(-) breast cancer cells at high doses
Endocrine disruptor-may have negative health effects like BPA
Heightened concern due to soy isolates being added to many food products in US & most being GMO
Genistein can promote tumor growth at low, physiological doses

11. Epidemiological Studies
Studies have shown that Asian women who regularly consume soy have a 3-5 fold lower risk for breast cancer than Caucasian women who do not regularly consume soy
Average daily intake of soy mg in Asian women and less than 1 mg in Caucasian women
Meta Analysis (Trock, 2006)
High soy intake associated w/ reduced breast cancer risk among Caucasian women living in the west, especially in pre-menopausal women, but not in Asian women living in Asia
Meta Analysis (Wu, 2008)
Significant reduction in breast cancer risk in Asian and Asian Amercian women consuming soy, but not in Caucasian women

12. Meta Analysis (2014) Premenopausal women
Compiled results of 30 studies showed soy isoflavone intake inversely associated with breast cancer risk in Asian countries, but not significant in Western countries
Soybean/Soy products > Soy Isoflavones
Postmenopausal women
Compiled results of 31 studies showed that highest intake of soy isoflavones vs. lowest intake could decrease breast cancer risk by 25%
Only a weak significant effect in Western countries
Soy may only exert a protective effect when consumed at a young age

13. Shanghai Breast Cancer Survival Study
Longitudinal, population based study
5,042 women diagnosed w/ primary breast cancer between years of age
Interviews at 6, 12, & 18 months
Measured soy consumption (FFQ)
Medicine use
Disease progression & survival status
Adjusted for variables related to soy food intake & lifestyle
Recruited 6 months after cancer diagnosis

14. Results
Soy food consumption after cancer diagnosis inversely associated w/ mortality & recurrence regardless of Tamoxifen use status
Association observed in ER(-) & ER(+) breast cancer patients
Did not vary by menopausal status
Those in highest quartile for soy consumotion had greater association w/ decreased mortality & recurrence than those in lowest soy food quartile who were taking Tamoxifen

15. Soy Isoflavones and Risk of Cancer Recurrence in a Cohort of Breast Cancer Survivors: Life After Cancer Epidemiology (LACE) Study (2009)
1,954 women diagnosed with stage 1 breast cancer from 1997 to (survivors) followed for 6.31 years
Mailed semi-annual or annual (after April 2005) health status update questionnaire
Reported events verified by medical records
General diet assessed with FFQ
14 Item Soy FFQ
Measured soy intake from supplements
FFQ: asked to rate the frequency that they ate certain foods & in what portion size (small, medium, large)

16. Soy Isoflavones and Risk of Cancer Recurrence in a Cohort of Breast Cancer Survivors: Life After Cancer Epidemiology (LACE) Study (2009)
Non-significant trend of decreased risk of breast cancer with increasing intakes of daidzein (p=0.20) & glycetin (p=0.10)
More apparent in post-menopausal women for daidzein (p=.08) & glycetin (p=.06)
Significant decreased risk of recurrence in women who used Tamoxifen and consumed diadzein (p=0.05)
Similar relationship w/ genistein & glycetin but non-significant
Women who had never used Tamoxifen & were in the highest percentile for isoflavone intake (above 95%) had a significant risk for recurrence
Decreased risk of recurrence for women with high isoflavone intake and ER+ or PR+ tumors, but not in ER- or PR- tumors

17. Soy Isoflavones and Risk of Cancer Recurrence in a Cohort of Breast Cancer Survivors: Life After Cancer Epidemiology (LACE) Study (2009)
Consumption of soy products after a cancer diagnosis in women who use Tamoxifen may be associated with a reduced risk of recurrence
Decreased recurrence in ER+ and PR+ cancer with high isoflavone intake
Is it the hormone receptor positivity, Tamoxifen use, or a combination of both that cause these effects?
Significant effects only seen for post-menopausal women-hormones?
Other lifestyle factors not considered in this study
Results cannot be generalized to women with more advanced stages of breast cancer
Low levels of soy intake (similar to Western diet)

18. Soy Processing Soy found in 60% of processed foods
Popular food additive as cholesterol free, rich in complex carbs, unsaturated fatty acids, high in fiber, and free of lactose

19. Soy processing influences growth of estrogen-dependent breast cancer tumors (2004)
Soy products consumed in Asian countries are minimally processed while soy products in USA are highly processed
Processing removes many of the bioactve compounds in soy
Methods
Female ovariectomized mice
Negative Control (NC)
Positive Control (PC)
Soy Flour + Mixed Isoflavones (SF + MI)  Least processed
Soy Molasses (SM)  crude extract
Novasoy (NS)  crude extract
Mixed Isoflavones (MI)
Purified Genistein (GI)
All diets contained same amount genistein
Tumor area and body weight recorded weekly

20. Soy processing influences growth of estrogen-dependent breast cancer tumors (2004)

21. Soy processing influences growth of estrogen-dependent breast cancer tumors (2004)
All diets stimulated growth of tumors, but not equally
Same amount genistein in each diet  other components of soy must play a role
How can this be?
Degree of processing could alter bioavailability & affect estrogenic potency of genistein content
Other compounds in soy act as antagonists to genistein
Protease inhibitors, phenolic acids, phytic acid, lignans, saponins, phytoestrols

22. Conclusion
Estrogen plays many roles in the female body & is of interest when females begin menopause
Phytoestrogens can act in the same way as estrogen in the body, but have a weaker effect
Soy has been reported to have many health benefits, while its esrogenic properties have posed risk
Conflicting results in Asian vs. Western populations
Possibly due to soy consumption early in life or processing of soy foods
Conflicting results based on menopausal status
Moderate consumption of soy considered safe amongst most populations, but may pose risks for individuals currently undergoing treatment for breast cancer