1. Soy Isoflavones and Their Effect on Breast Cancer
Presented by Tricia Bulatao
NTR 502: Advanced Food Science
The Sage Colleges, Troy, NY

2. Abstract
Breast cancer is the 2nd leading cause of death of American women. It is estimated that 1 in 8 American women will be diagnosed with breast cancer during their lifetime (American Cancer Society, 2013). Nearly 60% of all breast cancers are hormone-receptor positive or contain cancer cells with estrogen-receptors (American Cancer Society, 2013). Treatment for reducing the recurrence of these breast cancers include either blocking estrogen from bonding with the estrogen receptors or reducing the production of estrogen (American Cancer Society, 2013). Soy isoflavones are structurally similar to estrogen and behave like estrogen when metabolized in the body. In their metabolized form, they have been shown to compete with estrogen by binding to the estrogen receptors on the cell membrane (Pilsakova et al., 2010). Various factors influence the bioavailability and absorption of isoflavones. Intestinal microflora has been shown to metabolize isoflavones from their inactive glycosidic forms to their active aglyconic form (Gropper & Smith, 2013; Pilsakova et al., 2010). Fermented soy product contain isoflavones in their aglyconic form (Nagata, 21010). The ability to metabolize isoflavones into their aglyconic form, the presence of estrogen receptors and the amount of estrogen produced each contribute to the effectiveness of isoflavones in preventing and reducing the recurrence of breast cancer (Matthies et al., 2012; National Cancer Institute, 2013; Kang et al., 2010). There is no recommended dose or general advice with regards to consuming soy isoflavones to reduce the incidence and recurrence of breast cancer. Health care professionals should individualize their recommendations to the needs and status of their clients. Further research is needed on soy isoflavones to limit confounding factors as the potential benefits can greatly improve the lives of those at risk for and living with breast cancer.

3. Introduction
1 in 8 American women diagnosed with breast cancer (American Cancer Society, 2013).
60% of breast cancers are estrogen receptor positive (ER+) (American Cancer Society, 2013).
Treatment of ER+ breast cancer blocks estrogen from binding or reduces production of estrogen (American Cancer Society, 2013).
Soy isoflavones function like estrogen.

4. Structure of Isoflavones
Figure 1: Structure of the main isoflavones and 17-estradiol (Wallace et al., 2011)
Structure of Isoflavones
Polyphenolic plant compounds
Phytoestrogens – structure similar to estradiol
Structure of key isoflavones and 17-estradiol (Wallace et al., 2011)

5. Physiological Action of Isoflavones
Naturally occur in inactive glycosidic forms (Pilsakova et al., 2010)
Fermentation hydrolyzes inactive form into active form (Gropper & Smith, 2013; Pilsakova et al., 2010)
Daidzein and genistein are predominant soy isoflavones (Gropper & Smith, 2013)
5-hydroxy equol and equol are metabolites of isoflavones, greater affinity to ER vs. precursors (Matthies et al., 2009)

6. Isoflavone & Microflora
Metabolize genistein and diadzein into 5-hydroxy equol and equol in the intestines (Matthies et al., 2012)
Different bacteria metabolize different isoflavones (Matthies et al., 2009)
Rat study using Slackia isoflavoniconvertens showed 426- fold increase in daidzein metabolization vs. genistein (Matthies et al., 2012).
Intestinal microflora increase bioavailability & absorption.

7. Estrogen Receptors (ER) & Breast Cancer
Estrogen binds to ER cell proliferation
Cancer cells with ER will mutate or proliferate when stimulated by estrogen (National Cancer Institute, 2013)
Incidence of breast cancer vary with dietary soy intake (Nagata, 2010)
ER development varies with diet & lifestyle

8. Breast Cancer & Soy Isoflavones
Early exposure to soy in Japan associated with  incidence (Nagata, 2010)
Fermented soy (miso, natto) associated with  incidence (Nagata, 2010)
Synergistic effect of high soy intake with endocrine treatments (Kang et al., 2010; Li et al., 2013)
High soy intake associated with  recurrence & overall risk (Dong & Qin, 2011)

9. Breast Cancer & Soy Isoflavones continued
More equol producers among Asians & vegetarians (Franke et al., 2011). Consistent soy consumers.
Conflicting studies regarding high soy diet and equol producing status of individuals (Franke et al., 2011; Frankenfled et al., 2005 ).
Low estrogen levels isoflavones stimulate estrogen activity (Nagata, 2010)
High estrogen levels isoflavones block estrogen activity (Nagata, 2010)

10. Estrogen Levels, Isoflavones & Breast Cancer
Isoflavones compete with estrogen to bind to ER
High isoflavone intake had no impact on recurrence among pre-menopausal women (Franke et al., 2012)
High isoflavone intake decrease recurrence among post- menopausal women (Nagata, 2010)
Confounding factors : fruit & vegetable intake, BMI, exercise

11. Conclusion
No dose recommendations - confounding factors, concerns with high soy intake affecting existing cancer growth.
Higher soy intake levels & fermented forms of soy among Asians associated with reduced breast cancer
Consistent soy consumption  higher prevalence of equol producers.
Synergistic effect of soy intake with endocrine therapy of ER+ breast cancer patients.