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Soya and breast cancer: myths, controversies and the facts.
ulster.ac.uk
Dr Pamela MageeNorthern Ireland Centre for Food & Health
Alpro Foundation SymposiumUniversity of Giessen, 2nd December 2014
Soya and breast cancer - overview
• History of soya• Soya foods
• nutritional content
• consumption
• bioactives
• Isoflavones
• Soya and breast cancer prevention – the evidence
So a and breast cancer patients rec rrence• Soya and breast cancer patients – recurrence
• Conclusions and recommendations
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History of soya
Glycine max
L t f th f il• Legume - part of the pea family
• Consumed for ~5000 years
• First report 2838 BC in China - soya was one of 5 sacred crops
• Cultivated first in China then spread to Korea, Japan (8thC AD) d SE A i(8thC AD), and SE Asia
• First appeared in Europe & North America in 18th C
Soya foodsNon-fermented
• Edamame – immature soya beans in pod• Tofu – soya bean curdy• Roasted beans• Soya milk – heated water extract of ground beans
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Soya foods Fermented
NattoTempeh
Miso
Shoyu (soya sauce)
‘Western’ soya foods
• soya yoghurt• soya milk• soya milk• desserts – mousses, puddings, • custard, soy milk shakes
• Soya protein concentrates y(protein after removal of soya oil)
• Textured vegetable protein (TVP)
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Soya FoodsNutritional content
Soya beans:
• One of highest quality vegetable proteins• One of highest quality vegetable proteins
• Good source of PUFAs (e.g. -linolenic acid)
• Low in saturated fats
• Fibre
• Vitamins & minerals
Soya Food Consumption in Asia(Soya protein intake)
Japan: 6 – 12 g/day
t f i tt f i d t f- tofu, miso, natto, fried tofu
China (Shanghai): 12 – 30 g/day
- soya milk, tofu, processed soya products other than tofu
(Messina & Messina, 2010)
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Soya phytochemicals
• Isoflavones
• Saponins• Saponins
• Phenolic acids
• Phytic acid
• Enzyme-regulating proteins e.g. protease inhibitors
• sphingolipids
Soya Isoflavones
Similar in structure to 17-oestradiol Bind to ER/ER
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Myth 1
‘Isoflavones are Phytoestrogens’
• Much greater affinity for and more effectively transactivate ER in comparison to ERtransactivate ER in comparison to ER
• Classified as natural selective oestrogen receptor modulators (SERMs)
• SERMs have oestrogen-like effects in some tissues and either no effect or anti-oestrogenic effects in other tissues in which oestrogen receptors are present (e.g. tamoxifen, raloxifene)raloxifene).
Soya Isoflavones
Metabolism• 3 soyabean isoflavone
aglycones: genistein, g y gdaidzein and glycitein.
• Present in raw soya beans as -glycosides (genistin, daidzin, glycitin)
• During digestion the glycoside is hydrolyzed
Daidzin
glycoside is hydrolyzed biologically active aglycone
Daidzein
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Soya isoflavonesMetabolism
• Isoflavones have a short half-life (approx 8hrs)
• Excretion within 24 hrs of ingestion• Excretion within 24 hrs of ingestion
• Interindividual variation in bacterial metabolism of IFs in gut – variation in gut microflora
Inter-individual variation in isoflavonemetabolism.
Only ~ 30% of Western populations have the ability to convert daidzeinto equol following a soya challenge.
From Lampe JW (2009). Am J Clin Nutr; 89(suppl): 1664S-7S (with permission).
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Isoflavone content of soya foods and daily intake.
1g soya protein in traditional Asian soyfoods ~ 3 5mg isoflavones3.5mg isoflavones
Daily IF intake older Japanese adults 25 – 50 mg(Messina et al. JNCI 2006; 98 (18), 1275‐84)
IF intake in Europe/USA ≤ 3 mg/dIF intake in Europe/USA ≤ 3 mg/d(Messina. J Nutr 2010; 140, 1350S‐54S)
Soya and breast cancer - overview
• History of soya• Soya foods
• nutritional content
• consumption
• bioactives
• Isoflavones
• Soya and breast cancer prevention – the evidence
S d b t ti t• Soya and breast cancer patients – recurrence
• Conclusions and recommendations
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UK 87.9
Breast Cancer Incidence
Ireland 93.9
USA 93.9
China 21.6
Indonesia 36.2
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Breast Cancer Risk Factors
• Hormone-related:–Early onset of menarchea y o set o e a c e–Late onset of menopause–Delayed age of first pregnancy–Elevated free oestradiol concs in postmenopausal women
• Low incidence BCa in Asia associated with consumption of low fat high fibre high soya diet (Tham et al 1998)of low-fat, high-fibre, high-soya diet (Tham et al., 1998)
2
RR(a)
2
2,2RR(b)
Relative risk of breast cancer in women migrating from Asia to the USA by place of birth of the subject, her parents (a) and her grandparents (b)
(adjusted for ethnicity, study area and age).
Ziegler et al. J Natl Cancer Inst 1993;85(22):1819‐1827.
0 6
0,8
1
1,2
1,4
1,6
1,8
0 6
0,8
1
1,2
1,4
1,6
1,8
2
0
0,2
0,4
0,6
0
0,2
0,4
0,6
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Soya/isoflavone consumption and breast cancer risk.Epidemiological studies – meta-analyses
Ref. Studies RR (95% CI)
Wu et al. (2008) 1 cohort, 7 case‐control 0.71 (0.60‐0.85)
Dong & Qin (2011) 14 prospective studies 0.76 (0.65 – 0.86)
Xie et al. (2013) 7 cohort, 15 case‐control 0.70 (0.57 – 0.86)
Chen (2014) 35 studies (26 on pre‐ and post‐menopausal women, 4 on pre‐only and 5 on post‐ only)
0.75 (0.63 – 0.86)
Soya/isoflavone consumption is associated with a reduction in breast cancer risk of ~ 20-30% among Asian women.
Controversy 1
Soya isoflavone consumption does not reduce breast cancer risk in Western women.
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Breast Cancer Risk – Asian women (highest vs. lowest intake of isoflavones)
Xie et al. Asia Pac J Clin Nutr 2013;22(1):118‐127
Breast Cancer Risk – Western women (highest vs. lowest intake of isoflavones)
Horn-Ross (2001)
Wu (2002)
Silva (2004)
Keinan Boker (2004)
1.00 (0.79, 1.30)
0.61 (0.39, 0.97)
0.58 (0.33, 1.00)
0 98 (0 65 1 48)Keinan-Boker (2004)
Linseisen (2004)
Touillaud (2006)
Fink (2006)
Cotterchio (2008)
Travis (2008)
Hedelin (2008)
0.98 (0.65, 1.48)
0.85 (0.54, 1.33)
1.00 (0.76, 1.30)
0.95 (0.74, 1.02)
1.06 (0.87, 1.30)
1.17 (0.79, 1.31)
0.98 (0.83, 1.17)
O ll 0 97 (0 89 1 06)
Xie et al. Asia Pac J Clin Nutr 2013;22(1):118‐127
Overall 0.97 (0.89, 1.06)
0.33 1.00 3.00
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Asian vs. Western women
Author Asian Western
RR (95% CI)
Author Asian Western
Wu et al 0.71 (0.60-0.85) 1.04 (0.97-1.11)
Dong & Qin 0.76 (0.63-0.93) 0.97 (0.87-1.06)
Chen et al 0.59 (0.48-0.69) 0.90 (0.77-1.04)
Xie et al 0.70 (0.57-0.86) 0.97 (0.81-1.06)
Is the lack of effect in western populations perhaps due to low intake of isoflavones?
Isoflavone intake
• Japan and China - ~ 40mg/d
• USA, Europe < 3mg/d
(Messina, 2010)
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EPIC study (Oxford Cohort)
N=37,643 (with deliberate over-sampling of vegetarians)
Travis et al. Int J Cancer 2008; 122:705-710.
Why was there no observed protection against breast cancer with soya isoflavone consumption in EPIC study?
Is the lack of effect in western populations perhaps due to low intake of isoflavones?
Perhaps due to patterns of soya isoflavone intake.
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Early intake and breast cancer• Asian-American women living in USA
• 1248 breast cancer patients vs. 1148 controls
Intake Adoles / Adult Risk
Low / LowLow / Low
Low / High 9%
High / Low 28%
High / High 38%
Wu AJCN 89, 1145 2009
• Shanghai Women's Health Study
• 592 breast cancer patients from a cohort of 73 223
Intake Adoles / Adult Risk
Low / Low
Low / High 43%
High / Low 38%
High / High 59%
Lee AJCN 89, 1920 2009
Intake during adolescence and BCa risk.
• Shanghai Breast Cancer Study, 1996-1998
• 1459 cases, 1556 age-matched controls
Quintile OR (95% CI)
1 1.00
2 0.75 (0.60 – 0.93)
3 0.69 (0.55 – 0.87)
4 0.69 (0.55 – 0.86)
5 0.51 (0.40 – 0.65)
• Observed for both pre-menopausal and post-menopausal women
Shu et al. Cancer Epidemiol Biomarkers Prev 2001;10:483-488.
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Soya intake in childhood & BC risk
• Population based case control in Asian Americans
• 597 cases 996 controls• 597 cases, 996 controls
Age RR (95% CI) 3rd vs. 1st tertile
Child 5-11y 0.40 (0.18-0.83)
Adolescent 12-19y 0.80 (0.59-1.08)
Adult 20+ 0.76 (0.56-1.02)
Effects seen were not influenced by race (Japanese, Filipino, Chinese) or country of birth (Asia / USA)
Korde et al CEBP18, 1050, 2009
Pre vs. post menopausal BC
0,9 Pre
0 2
0,3
0,4
0,5
0,6
0,7
0,8Post
RR
0
0,1
0,2
Wu 2008 Dong 2011 Xie 2013 Chen 2014
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Soya and breast cancer - overview
• History of soya• Soya foods
• nutritional content
• consumption
• bioactives
• Isoflavones
• Soya and breast cancer prevention – the evidence
• Soya and breast cancer patients – recurrenceSoya and breast cancer patients recurrence
• Conclusions and recommendations
Controversy 2
Soya may increase the risk of recurrence in breast cancer survivors.
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Soya for breast cancer survivors.
• Concern following animal studies demonstrating that isoflavones stimulated breast cancer cell growth inisoflavones stimulated breast cancer cell growth in animal models.
• For example: dietary genistein MCF-7 oestrogen-dependent tumours (Hsieh et al., 1998).
• Now know animals metabolise isoflavones differently from humans (Setchell et al. AJCN 2011;94:1284-1294).
Magee & Rowland. Curr Opin Clin Nutr Metab Care 2012, 15:586–591
• Soya consumption - no detrimental effects on risk of recurrence and may actually reduce risk.
• Soya does not interfere with tamoxifen or anastrazole.
• Women at increased risk of BCa due to genetic• Women at increased risk of BCa due to genetic polymorphisms may especially benefit from soya consumption.
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5 cohort studies (USA & China)
• Guha 2009 Br Canc Res Treat 118, 395 2009 (Life After Cancer
Post diagnosis soya intake and death/BC recurrence – meta-analysis
Guha 2009 Br Canc Res Treat 118, 395 2009 (Life After Cancer Epidemiology) (USA)
• Caan CEBP 20, 854, 2011 (Women’s Healthy Eating & Living (USA)
• Shu JAMA 302, 2437, 2009 (Shanghai Breast Cancer Survival Study)
• Zhang Asia Pacific J Cancer Prev 13, 475 2012 (China)
• Kang CMAJ 182, 1857 2010 (China)Kang CMAJ 182, 1857 2010 (China)
Chi et al 2013 Asian Pacific J Cancer Prev 14: 2407, 2013
11,206 patients; 948 deaths, 1449 recurrences
Median follow up: 3.9-7.3 years
Pre / Post menopausal, ER+/ER-, Tamoxifen use / non-use
HR (95% CI) for high vs. low soya food intake (quartiles)
Recurrence 0.74 (0.64 - 0.85)
Mortality 0.84 (0.71 – 0.99)
(q )
Chi et al 2013 Asian Pacific J Cancer Prev 14: 2407, 2013
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Chi meta-analysis
HR & 95% CI
0.840Death
0.740Recurrence
HR (95% CI) high vs. low soya intake group
Effect of ER receptor status and menopause on soya and BC recurrence
End-pointReceptor status
Menopausalstatus
ER- ER+ Pre Post
Recurrence0.64
(0.44-0.94)0.81
(0.63-1.04)0.91
(0.72-1.14)0.67
(0.56-0.80)
Mortality 0.70(0.58-0.84)
0.74(0.60-0.91)
0.78(0.69-0.88)
0.81(0.73-0.91)
Chi et al 2013 Asian Pacific J Cancer Prev 14: 2407, 2013
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Tamoxifen and Anastrazole interactions with soya intake.
Tamoxifen (Chi meta-analysis)End-point All Tamoxifen users
Recurrence 0.74 (0.64-0.85) 0.90 (0.48-1.47
Mortality 0.84 (0.71-0.99) 0.26 (0.06-1.10)
Anastrazole (Kang et al – Chinese BC patients)Intake Q1 Q2 Q3 Q4
HR (95%CI) 1.00 0.72 (0.56‐0.92)
0.71(0.54‐0.88)
0.65(0.47‐0.85)
(Q1 <15.2 mg IF/d; Q4 >42 .3mg IF/d)
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Soya and BCa survivors.
• Moderate soya consumption is safe for breast cancer survivors.survivors.
• Moderate consumption: 1 to 2 standard servings daily of whole soya foods e.g. tofu, soya milk, edamame, soya nuts.
• One serving ~ 7 g protein (25 mg isoflavones).
Conclusions.
• Meta-analyses demonstrate that soya isoflavoneconsumption is associated with a modest (~20 – 30%)consumption is associated with a modest ( 20 30%) reduction in breast cancer risk in Asian populations with little effect observed among western populations.
• Soya consumption during childhood and adolescence confers greater protection against breast cancer risk (~60% reduction in risk).
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Conclusions (contd.)
• Concerns that soya consumption by breast cancer patients might exacerbate the disease are unfounded.patients might exacerbate the disease are unfounded. Soya foods (at Asian intake levels) have no detrimental effects on risk of recurrence or mortality and in some cases significantly reduce the risk.
• Soya does not appear to affect tamoxifen or anastrozoletherapy.
Acknowledgements:Prof. Ian Rowland
