This study found a significant 18% reduction in breast cancer risk in association with the above median soy isoflavone intake (
), a degree of risk reduction compatible with the results that we found in a combined analysis of eight studies in Asian populations with soy intake (Wu et al, 2008
). The amount of soy isoflavones (~10
mg per day) implicated to have benefit in cancer prevention can be obtained in one standard serving of tofu (Trock et al, 2006
). The inverse association with soy intake in this Singapore cohort was statistically significant in postmenopausal but not in premenopausal women (), but we were limited in studying such women by the lower age limit of this cohort study being 45 years, and only 26% of participants were aged 45–50 years at enrollment. There is a suggestion that heavier postmenopausal women showed a stronger association than leaner women, although the two sets of RRs are not statistically different from each other (). The risk reduction with soy intake was found in both ER+ and ER− tumours as well as in PR+ and PR− tumours (). A stronger soy–breast cancer association was found among women with longer (10+ years) duration of follow-up ().
To date, eight cohort/nested case–control studies have investigated the association between soy intake and breast cancer risk, of which four were not very informative, being conducted in western populations with very low soy intake (average of ~1
mg of soy isoflavones per day). Of these, no association was found in three studies in populations with very low soy intake (Horn-Ross et al, 2002
; Keinan-Boker et al, 2004
; Touillaud et al, 2006
), whereas one study found an increased risk (Grace et al, 2004
The other four cohort studies were in populations with moderate-to-high soy intake, one in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford), one of the few non-Asian populations with moderate soy intake. The mean daily soy isoflavone intake was 2.9
mg among non-vegetarians and 10.2
mg among vegetarians, but only about 30% of the 37
643 cohort participants were vegetarians, limiting the investigation of this question (Travis et al, 2008
). Three studies were conducted in Japan (Key et al, 1999
; Yamamoto et al, 2003
; Nishio et al, 2007
) with high soy intake. Our finding of a significant inverse association between soy intake and breast cancer, particularly in postmenopausal women is similar to that reported in the Japan Public Health Center-Based Prospective Study (JPHC) (Yamamoto et al, 2003
). Soy intake in the JPHC study was obtained using a validated FFQ including intake of five soy foods, covering approximately 90% of the total soy isoflavone intake in Japan (Yamamoto et al, 2001
). In contrast, breast cancer risk was unrelated to soy intake in two other Japanese cohort studies (Key et al, 1999
; Nishio et al, 2007
); assessment of soy intake was less complete in both studies and considerable random misclassification of soy exposure is likely to have led to underestimation of risk (ie, bias towards the null).
After the menopause, adipose tissue is the major site for oestrogen synthesis and high body size is associated with the elevated endogenous oestrogen (Judd et al, 1982
). We noted a stronger association among postmenopausal women with below vs
above median BMI, although the two sets of RRs were not statistically different from each other. In a case–control study among women in Shanghai, China, the inverse association was more evident in women with higher BMI (25+
) than women with lower BMI irrespective of menopausal status (Dai et al, 2001
). In the four cohort studies reviewed in the previous paragraph, the soy–breast cancer association was not examined separately by BMI category.
Our results show comparable effects of soy on ER+ and ER− tumours as well as PR+ and PR− tumours (). Of the eight studies included in our meta-analysis on soy and breast cancer in Asian populations (Wu et al, 2008
), only one study in our meta-analysis investigated the risk by hormone receptor status, finding the effect more apparent for tumours that were positive for both ER and PR (Dai et al (2001)
. Further investigation of the soy–breast cancer association by menopausal status and ER/PR status will be needed.
Three studies (Shu et al, 2001
; Wu et al, 2002
; Thanos et al, 2006
), including a case–control study that we conducted among Asian American women in Los Angeles County, found that the timing of soy exposure is an important codeterminant of risk, with stronger effects from exposures at earlier ages. This study lends further support to soy exposures occurring during the earlier stages of carcinogenesis and would result in a greater degree of reduction in a woman's subsequent risk for breast cancer. We noted that the magnitude of risk reduction among women with 10 or more years between exposure assessment and cancer diagnosis was twice than that among their counterparts with shorter time intervals. Interestingly, this model may explain the seemingly contradictory findings from recent soy intervention studies with generally null findings (Maskarinec et al, 2004
; Wu et al, 2005
This prospective study has several important strengths. First, information on soy intake and other risk factors was obtained in-person before cancer diagnosis and thus the recall bias is not a concern. This is particularly important as seven of the eight studies in our meta-analysis on soy and breast cancer were case–control studies (Wu et al, 2008
). Second, we used a validated FFQ, our assessment of soy intake was relatively complete, and dietary intake of soy was statistically significantly correlated with urine isoflavone levels (Seow et al, 1998
). Third, our study is larger than previous cohort studies on this topic (two of the previous studies had less than 200 breast cancer cases (Yamamoto et al, 2003
; Nishio et al, 2007
). The larger sample size, particularly of postmenopausal women, has allowed us to investigate the potential modifying effect of body size on the soy–breast cancer association in postmenopausal women. Finally, we were able to examine the risk pattern by hormone receptor status, apparently the first such from a prospective study.
In summary, among 34
028 women in the SCHS, high soy intake (
mg isoflavones per 1000
Kcal) was associated with a significant 18% reduction in breast cancer risk. Our results adds to the compelling results obtained from case–control studies on soy and breast cancer and suggest that the soy isoflavones may have lasting beneficial effects against breast cancer development. The level of soy isoflavones implicated to have benefit (~10
mg isoflavones per day or one standard serving of tofu) is achievable even in populations that do not typically eat soy foods.