Adolescent Soy Intake And The Risk Of Breast Cancer:a Systematic Review

BACKGROUNDBreast cancer is one of the most common malignant tumor women in recent years, its incidence is increasing year by year. The American Cancer Society’s estimates indicate that approximately1.3million new cases of invasive breast cancer were diagnosed globally in2007and nearly500,000died from this disease, which represents about23%of all female cancers, making breast cancer the most common cancer among women. Adding to the impact of the breast cancer burden is the psychological trauma often associated with the surgery to treat this disease,and quality of life after breast cancer is poor. However, there is a huge variation in breast cancer incidence rates among countries and regions worldwide. For example, the age-adjusted breast cancer incidence and mortality rates per100,000person years for North America (99.4and19.2, respectively) are about5times higher than the rates in Asia (22.1and8.8, respectively), but the rates rapidly increase in Asian women following emigration to the United States. Changes in cancer risk following emigration are thought to reflect lifestyle changes, particularly in dietary patterns, many observations have led to a search for protective factors in the Asian diet. Numerous epidemiological studies focusing on dietary fat and breast cancer association have found no association between dietary fat intake and breast cancer risk.In1991, when the U.S. National Cancer Institute first started a request for applications calling for the study of the role in soy in reducing risk of breast cancer, this topic has been repeatedly investigated. Up to now, at least30epidemiologic and40animal studies have investigated the soy and breast cancer relationship.The results show, isoflavones, a class of phytoestrogens abundant in soy foods, exert weak estrogenic effect and have anti-carcinogenic properties. A number of retrospective and prospective epidemiologic studies examining the association between dietary soy foods or isoflavones intake and risk of breast cancer have yielded inconsistent results.In2006, Trock published a meta-analysis of the epidemiologic data that included18studies and reported that high soy intake was modestly associated with reduced breast cancer risk, but the association was not statistically significant among women in Asian countries, and the inverse association between soy exposure and breast cancer risk was somewhat stronger in premenopausal women than in postmenopausal women.However, a more recent meta-analysis that included19studies by Wu et al. found there was a marked significant trend of decreasing risk with increasing soy food intake in Asian and Asian American, in contrast, soy intake was unrelated to breast cancer risk in studies conducted in Western women. In2011, a most resent meta-analysis of14prospective studies, suggests soy isoflavones intake is associated with a significant reduced risk of breast cancer incidence in Asian women, but not in Western women. Many animal studies do not support an association between exposures to this phytoestrogen during adulthood and reduced mammary tumorigenesis. The protective role of soy intake during adulthood is further questioned by the results obtained in intervention studies. A meta-analysis included8randomized controlled trials compared isoflavones with placebo for between6months and3years, suggested Isoflavone intake does not alter breast density in post-menopausal women, but may cause a small increase in breast density in premenopausal women. Mammographic density is a biomarker of increased breast cancer risk; high density increases the risk by four-to sixfold. Migration studies have suggested early life environmental exposures have a profound impact on breast cancer risk. One possible explanation for the discrepancy between the protective role of soy found in three meta-analyses and the lack of effect on biomarkers of breast cancer risk or the results generated in animal studies or the randomized controlled trials during adult exposure to soy/isoflavones is that, to be protective, this bioactive food component may need to be consumed during early life. There are some animal studies support this argument, furthermore, epidemiological studies indicate that adolescence exposure to soy provides protection against breast cancer later in life. Because the data show risk-enhancing as well as risk-reducing effects of genistein and soy, it is important that associations between adolescence exposure to soy and breast cancer risk be rigorously evaluated before recommendations can safely be made, Therefore, we conducted a meta-analysis to explore in detail the epidemiologic evidence relating consumption of adolescence exposure soy foods to risk of breast cancerOBJECTIVE1. Retrieving, searching the current papers on the efficacy of assumpting soy foods on the incidence of female breast cancer, evaluate the quality systematicly.2. Evaluate the efficacy of assumpting soy foods on female breast cancer in adolescence.3. Evaluate the differences of the efficacy on the female pre-menopausal breast cancer and postmenopausal breast cancer intaking soy foods in adolescence systematically.4. Evaluate the differences of the efficacy on the eastern female breast cancer and western female breast cancer intaking soy foods in adolescence systematically.METHODS1. Search strategy We conducted a systematic literature search of the Cochrane Library, MEDLINE, EMbase, VIP, CNKI, WanFang Database, CBM and Google Scholar from the date of their establishment to August2011by using the following English and Chinese search terms:"adolescent,""adolescence,""soybeans,""soy foods,""isoflavones,""phytoestrogens,""breast cancer,"and“青春期”,“豆类食品”，“大 豆”,“大豆异黄酮”,“植物雌激素”,“乳腺癌”。 We also carried out a manual search using reference lists of original articles and recent reviews. Not only full-length original journal articles were considered, but some attempt was also made to include abstracts or unpublished studies.2. Study selection Studies were eligible for our analysis if:(1) the study design is case-control study or cohort study;(2) data related to adolescent dietary consumption of soy isoflavones were available;(3) the endpoint was breast cancer incidence;(4) the association of isoflavones with breast cancer risk was specifically evaluated; and (5) relatively complete assessment of total isoflavones intake was performed.3. Data extraction and quality evaluation: We recorded study characteristics as follows:(1) name of first author, publication year, and country of origin;(2) study design and endpoint;(3) length of follow-up;(4) number of cases and controls;(5) confounders adjusted for in multivariate analysis;(6) relative risk (RR), or odds ratio(OR) from the most fully adjusted model for the highest versus the lowest soy exposure and their corresponding95%confidence interval (95%CI). RR is used to represent ratio measures of effect, including hazard ratio and odds ratios. Quality evaluation:Evaluate the studies according to methodology and comprehensive quality.4. Statistical analysis We investigated the associations between the overall adolescent soy isoflavones intake and the risk of breast cancer incidence. Homogeneity of effect size across studies was tested by Q statistics (P<0.10). We also computed the I2, a quantitative measure of inconsistency across studies. If substantial heterogeneity exists, the random-effects model is appropriate; otherwise, the fixedeffects model is preferred. Pre-specified stratified analyses were performed to assess the impacts of various study characteristics, including menopausal status and regions on outcomes. A sensitivity analysis was conducted using both fixed-and random-effects models to evaluate the robustness of results. The potential publication bias was examined by Egger’s test (P<0.10). All analyses were performed using STATA version11.0(Stata Corp, College Station, Texas). A P value<0.05was considered statistically significant, except where otherwise specified.RESULTS1Characteristics of the included studies Six studies met the inclusion criteria after our complete review. Two studies that captured a part of total soy foods in those populations were excluded due to incomplete assessment of isoflavones intake. The studies eligible for analysis were published between1998and2009. Two studies from Asia,4from North America. Of the6papers,5papers were case cantrol studies, and only one study was cohort study.2Bias risk of the included studies The quality evaluations which research the separate bias risk and methodology, utilize the Non-randomized study bias risk assessment methodology(NOS) recommended from Cochrane assist Mesh to evaluate, during the selection of study objects, the cohort study evaluates the representativeness of exposure group, representativeness of non-exposed group, determining method of exposure factors and whether there is result index we need during result measurement; whether they are comparable between groups; the completeness of evaluation methods, follow-up time, exposure group and non-exposed group follow-up during results measurement. During the selection of study objects, the case control study evaluates whether the case selection is appropriate, representativeness of case, selectiong of reference, fix of reference; whether they are comparable between groups, exposure factors determining method during exposure factors measurement, wether utilize the same methods to determine case group and exposure factors of comparable group, whether report the non-response rate, whether the non-response rates are the same between the case group and comparable group. Utilize the NOS to evaluate bias risk of each study syntheticly, scores as below: Potischman’s study got7, Shu’s study got8, Wu’s study got7, Thanos’s study got7, Korde’s study got7, Lee’s study got8, they are all research with high quality and low bias.3Among6Studies involving6609patients and79538controls. The results of meta-analyses of all women showed that high soy intake in adolescent was modestly associated with reduced breast cancer risk (OR:0.816,95%CI:0.670-0.993)We did the subgroup analysis according to the menopausal status of the object of study when breast cancer happened, United the OR value to0.661(95%CI:0.550-0.796) in premenopausal women, and the OR value to0.782(95%CI:0.486-1.259) in postmenopausal women, This means that Intake of soyfood in adolescence can protect the premenopausal breast cancer but not postmenopausal breast cancer. Because this study focus on the diet in adolescence, the age is small, we defined the Asian-American women as eastern population of study, in different population of study, we did subgroup analysis and found that there is little difference in the negative relationship between the intake of soyfood in adolescence and the incidence of breast cancer in eastern population(OR:0.793,95%CI:0.569-1.105), compared with that in western population(OR:0.837,95%CI:0.743-0.943).In the6studies, Lee’s type of study is cohort study, the last is case-control study, so it did not affect our result of study substantially after deleting Lee’s study, The intake of soyfood in adolescence can still decrease the risk of incidence of breast cancer effectively(OR:0.730,95%CI:0.591-0.902); Potischman’s study in1998is the earliest one, and only his study did not compare the baseline conditions, so it did not affect our study substantially after deleting his study, The intake of soyfood in adolescence can still decrease the risk of incidence of breast cancer effectively(OR:0.799,95%CI:0.632-1.009).Finally, according to Egger’s test, we did Linear regression analysis utilizing standard normal deviation as variable and standard error as Independent variables. We found the intercept is-0.18, and there is no statistically significant difference after t test (t=0.07, P=0.944), that means there is no publication bias.CONCLUSION1. Soy intake in adolescent may be associated with a small reduction in breast cancer risk.2. By subgroup analysis, we found that high soy intake in adolescent was modestly associated with reduced premenopausal women breast cancer risk.3. By subgroup analysis, the Protective effect of high soy intake in adolescent was not significant difference between east people or west people.4. The quantity and quality of the included studies were inadequate, in particular, the methodology defects of case-control study, and therefore we need more high-quality follow-up period longer cohort study to increase the strength of evidence.