Soy Isoflavones & Breast Cancer Risk: A Systematic Review

A Presentation in Partial fulfillment of FDNT565

Presenter: Jannel Gentius
Professor: Dr. Tony Jehi
 Introduction

231,840 new cases

95% >40 years of age
Menopausal - Post-
menopausal women
Higher mortality rates –
Black women
Risk Factors

Female sex, Race,

Genetics, Physical
inactivity, diet

Inverse relationship

Low-fat, plant-based
diets and cancer risk

Soy isoflavones
consumption
 Introduction Cont’d
Inconsistent findings
Soy has beneficial effects on
adipocytokines
Soy was inversely associated with
circulating levels of (IL-6) and tumor
necrosis
Soy stimulate nipple aspirate fluid
(NAF)
Objective of Review
Evaluate the evidence - association
between intake of soy isoflavones
and the risk of breast cancer among
pre-and post-menopausal women
 Methodology
Ebscohost

Academic Search
Complete,MEDLINE

Google Scholar

Human Intervention

Observational Studies

Pre and Post-menopausal

women
Inclusion

X
Intervention & observational
studies, Soy foods

Exclusion

Animal studies, In vitro in

vivo

Soy supplements, Co-existing

X
conditions

Diminished autonomy,
Alternative cancer treatment
Search for “soy isoflavones and risk of breast
cancer” in Ebscohost platform (ASC and
MEDLINE) and google scholar:
Literature Flow Chart
- Ebscohost – 464
- Google Scholar – 15, 700
Soy dsdsad

Search strategy refined for time period 2010-

2020 and additional keywords “pre-
menopausal and post-menopausal” yielded:
- Ebscohost – 144
- Google Scholar – 17
 

Further filtering and screening to display only

records from scholarly peer reviewed journals
and full text:
- Ebscohost – 33
- Google Scholar – 14
 
Publications excluded because they did not
meet inclusion criteria, were not in English or
were duplicate studies (n=25)
Publications retained for full evaluation
(n=22)
Publications excluded because they strayed to
much from the objective of the review (n=12)

Publications included in the systematic

review (n=10)
- 3 Randomized Control Trials
- 4 Case-control studies
- 3 Prospective Cohort studies Figure 1 Flowchart illustrating movement of papers from search to inclusion.
 AUTHORS OBJECTIVE
RANDOMIZED CONTROLS
(Nadadur, et al, 2016 Investigate the effects of soy
foods(50mg) on adipocytokines
(Maskarinec, et al., 2011 Examine the effect of soy food on
nipple aspirate fluid production
9Morimoto, et al., 2012) Examined the
effect of soy foods on the 2:16α-OH
CASE CONTROLS
Zhu, et. Al, 2011 Investigate the association between
soy food intake and reduced risk of
breast cancer.
Zhang, et al., 2010
Wang et al., 2011
Cho et al., 2010
PROSPECTIVE COHORT
Wei, et al., 2019 investigate the association of soy
intake with breast cancer risk
Bagglia et al., 2016
Wada, et al., 2013
STUDY POP
Post-menopausal women from USA
with varying ethnic background
Post-menopausal women from USA
of varying ethnic background
Pre-menopausal women from
Hawaii of diverse ethnicities.
Chinese pre-and-post-menopausal
women
Chinese women
Korean women
Chinese women
Japanese women
KEY FINDINGS
No statistically significant
differences of adipocytokine levels
between experimental and control
groups
No effect of the high-soy diet on
NAF volume (after 6 months P =
0.50 for diet; p-interaction = 0.21 for
diet with time).
No significant increase in the 2:16α-
OH E1 ratio (p=0.05)
Soy intake was associated with a
46% to 64% decrease risk of breast
cancer
Inverse associated 0.54 (0.34–0.84)
between soy intake risk of breast
cancer
Inverse association between soy
intake and breast cancer risk
higher soy intake inversely
associated with
the risk of breast cancer in HR
(95% CI) of 0.76 (0.60–0.96)
Breast cancer lower
among women with higher intakes
of soy
 Results
Randomized Control Studies

no beneficial effects on adipocytokines, (p=0.97; p = 0.67,

p=0.21; p=57)

nipple aspirate fluid show no significant increase with a

high soy diet (p = 0.50

no compelling significant increase in 2:16alpha-OH E1

ratio (p=0.05)

Case Control Studies

The highest, relative to lowest soy isoflavone intake was

associated with a 46% to 64% decrease risk of breast cancer
 Results
Prospective Cohort

for highest versus lowest quintile soy intake soy

consumption was protective of breast cancer risk
8(HR=0.78, 95% CI=0.63-0.97) for all women (Baglia, et
al., 2016).

Effects on Pre and Post menopausal Women

In some instances, this association was predominantly seen

in premenopausal women (HR=0.46; 95% CI:0.29-0.74),
trend test P < 0.001)
 Results
Effects of Soy by Receptor Genes

reduced risk for breast cancer was observed for ER+/PR+

women with highest soy protein intake (OR=0.63,
95%CI=0.45-0.97 in all women)

High soy intake showed protective effects of breast cancer

among postmenopausal women carrying CYP1B1 Val/Val
(aOR.0.24, 95% CI: 0.07–0.89) and CYP1B1 Val/Leu
(aOR.0.25, 95% CI: 0.08–0.82))
 Mechanisms

Decline of hormones after

menopause modifies the
effect of soy in breast
cancer carcinogenesis
isoflavones have anti-
oxidative anti-
inflammatory anti-
proliferative, and anti-
angiogenic properties
 Strengths and Limitations
Strengths

Review is that it examined both intervention and observational studies

Focus on only soy foods and not supplements gives greater efficacy to
the study

Limitations

Few studies (10)

Difficulty in making comparisons among studies

Varying populations

Dose-response relationships could not be established for all studies.

 Overall Findings

Soy food consumption is

therefore protective
against breast cancer -
inverse association
Effect seems to be greater
among post-menopausal
women
No significant findings in
RCTs
 Public Health Implications &
Recommendations
Public Health Implications

Reevaluation and reconsider proscriptions against soy foods

for breast cancer patients

Effect of soy on CYP1B1 gene opens the door to understand

the role of soy in nutritional genomics.

Recommendations

Investigate the mediating or moderating effects of receptor

sites and genes on the association between soy consumption
and breast cancer risk.

More studies of various designs in particular intervention

studies are needed
 References
Baglia, M. L., Zheng, W., Li, H., Yang, G., Gao, J., Gao, Y. T., & Shu, X. O. (2016). The association of soy food consumption with the risk of subtype of breast cancers defined
by hormone receptor and HER2 status. International journal of cancer, 139(4), 742–748. https://doi.org/10.1002/ijc.30117

Cho, Y. A., Kim, J., Park, K. S., Lim, S. Y., Shin, A., Sung, M. K., & Ro, J. (2010). Effect of dietary soy intake on breast cancer risk according to menopause and hormone
receptor status. European Journal of Clinical Nutrition, 64(9), 924-932. doi:10.1038/ejcn.2010.95

Maskarinec, G., Morimoto, Y., Conroy, S. M., Pagano, I. S., & Franke, A. A. (2011). The volume of nipple aspirate fluid is not affected by 6 months of treatment with soy foods
in premenopausal women. The Journal of nutrition, 141(4), 626–630. https://doi.org/10.3945/jn.110.133769

Morimoto, Y., Conroy, S. M., Pagano, I. S., Isaki, M., Franke, A. A., Nordt, F. J., & Maskarinec, G. (2012). Urinary estrogen metabolites during a randomized soy
trial. Nutrition and cancer, 64(2), 307–314. https://doi.org/10.1080/01635581.2012.648819

Nadadur, M., Stanczyk, F. Z., Tseng, C.-C., Kim, L., & Wu, A. H. (2016). The Effect of Reduced Dietary Fat and Soy Supplementation on Circulating Adipocytokines in
Postmenopausal Women: A Randomized Controlled 2-Month Trial. Nutrition & Cancer, 68(4), 554–559. https://doi-org.ezproxy.andrews.edu/10.1080/01635581.2016.1158294

Wada, K., Nakamura, K., Tamai, Y., Tsuji, M., Kawachi, T., Hori, A., … Nagata, C. (2013). Soy isoflavone intake and breast cancer risk in Japan: From the Takayama
study. 133(4), 952–960. https://doi.org/10.1002/ijc.28088

Wang, Q., Li, H., Tao, P., Wang, Y.P., Yuan, P. et al. (2011) Soy Isoflavones, CYP1A1, CYP1B1, and COMT Polymorphisms, and Breast Cancer: A Case–Control Study in
Southwestern China. (2011). DNA and Cell Biology, 30(8), 585-595. doi:10.1089/dna.2010.1195

Wei, Y., Lv, J., Guo, Y., Bian, Z., Gao, M., Du, H., . . . the China Kadoorie Biobank Collaborative, Group. (2019). Soy intake and breast cancer risk: a prospective study of
300,000 Chinese women and a dose–response meta-analysis. European Journal of Epidemiology. doi:10.1007/s10654-019-00585-4

Zhang, C., Ho, S. C., Lin, F., Cheng, S., Fu, J., & Chen, Y. (2010). Soy product and isoflavone intake and breast cancer risk defined by hormone receptor status. 101(2), 501–
507. https://doi.org/10.1111/j.1349-7006.2009.01376.x

Zhu, Y.Y., Zhou, L., Jiao, S.C., & Xu, L.Z. (2011) Relationship Between Soy Food Intake and Breast Cancer in China. Asian Pacific Journal of Cancer Prevention, 12(11),
2837-2840.
Thank you!