Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review

May combine two claims.

Of 11 prospective cohort studies reporting on risk of primary breast cancer, one (9%) showed soy isoflavone intake was associated with overall reduced risk, while the remaining studies showed no associations.

“Of 11 studies reporting on risk of primary breast cancer, one (9%) showed that soy isoflavone intake was associated with overall reduced risk of breast cancer [116], while the remaining studies showed no associations [99,104,105,107-109,111,113-115,117].”

• cites [116] S Yamamoto, 2003, Soy, isoflavones, and breast cancer risk in Japan, J Natl Cancer Inst sourceNot checked — no full text of the source
• cites [99] TM Brasky, 2010, Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) Cohort, Cancer Epidemiol Biomarkers Prev sourcePartly supported

  The Abstract Results and Results sections report no association between soy-containing supplement use and breast cancer risk, supporting this paper's place among the studies cited for a null finding. The study measured soy supplement use, however, not soy isoflavone intake specifically, so it does not fully support that description of the exposure. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [104] M Hedelin, 2008, Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women, J Nutr sourceSupported
• cites [105] PL Horn-Ross, 2002, Recent diet and breast cancer risk: the California Teachers Study (USA), Cancer Causes Control sourceSupported
• cites [107] L Keinan-Boker, 2004, Dietary phytoestrogens and breast cancer risk, Am J Clin Nutr sourceNot checked — no full text of the source
• cites [108] TJ Key, 1999, Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan, Br J Cancer sourcePartly supported

  The Results (p. 3) report no significant association between tofu or miso soup consumption and breast cancer risk, supporting this paper's placement among the studies with no observed association. The Discussion (p. 8) says the questionnaire could not estimate soya isoflavone intake, so the paper does not directly support the claim about isoflavone intake. (LLM, conf=0.88)

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• cites [109] SA Lee, 2009, Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study, Am J Clin Nutr sourcePartly supported

  The Results (Table 2) report an inverse association between isoflavone intake and overall breast cancer risk, but the overall trend was not statistically significant. The Abstract reports a significant reduction specifically for premenopausal breast cancer, not for breast cancer overall. This source therefore supports a reduced-risk finding only with that narrower qualification. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [111] K Nishio, 2007, Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study, Cancer Causes Control sourceCould not verify

  The indexed copy for this DOI contains an erratum about boron and prostate cancer (Cancer Causes & Control 18:583–584), not the stated soy-food cohort study. Searches for soy isoflavones and reduced breast-cancer risk found no relevant passage, so the finding attributed to [116] cannot be checked against our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured
• cites [113] MS Touillaud, 2006, No association between dietary phytoestrogens and risk of premenopausal breast cancer in a French cohort study, Cancer Epidemiology, Biomarkers and Prevention sourceNot checked — no full text of the source
• cites [114] RC Travis, 2008, A prospective study of vegetarianism and isoflavone intake in relation to breast cancer risk in British women, International Journal of Cancer sourceDisputed

  The cited paper reports the opposite of the finding attributed to it. In “Isoflavone intake and breast cancer risk,” it finds no association between dietary isoflavone intake and breast cancer risk; the reported hazard ratios for moderate and high intake do not show an overall reduction. (LLM, conf=0.92)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Among all studies, there was report of only one case of breast cancer recurrence that occurred in a soy-allocated subject; and two new cases of breast cancer and one case of endometrial cancer among soy allocated subjects compared to five in control subjects.

“Amongst all the studies, there was report of only one case of breast cancer recurrence that occurred in a soy-allocated subject [142]; and two new cases of breast cancer and one case of endometrial cancer among soy allocated subjects compared to five in the control subjects [132,145,147,160].”

• cites [142] E Nikander, 2004, Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer, Journal of Clinical Endocrinology and Metabolism sourceNot checked — no full text of the source
• cites [132] FM Steinberg, 2011, Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women, Am J Clin Nutr sourceNot checked — no full text of the source
• cites [145] G Maskarinec, 2004, Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women, Cancer Epidemiol Biomarkers Prev sourceNot checked — no full text of the source
• cites [147] G Maskarinec, 2002, A randomized isoflavone intervention among premenopausal women, Cancer Epidemiology, Biomarkers and PreventionNot checked — no full text of the source
• cites [160] SA Khan, 2012, Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial. Cancer, Prev Res (Phila Pa) sourceDisputed

  Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

The Atkinson trial was assessed as having low risk of bias in approximately half of the categories but failed to provide adequate information to assess selection bias, detection bias, and attrition bias.

“The trial by Atkinson was assessed as having low risk of bias in approximately half of the categories but failed to provide adequate information to assess for selection bias, detection bias, and attrition bias [165].”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourceDisputed

  The Methods (Intervention and randomization; Mammographic density) describe random-number generation, who handled randomization, and blinding of researchers, participants, and radiologists. The Results (Withdrawals and baseline data) give the number and reasons for withdrawals and compare withdrawals between groups. The paper does not make the cited risk-of-bias assessment, and its reporting runs contrary to the claim that it lacked adequate information on detection and attrition bias. (LLM, conf=0.78)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

May combine two claims.

Caan et al reported a trend toward decreased risk of death among tamoxifen users with intake of total isoflavones ≥6.3mg per day (median 26.7mg), HR 0.26 (0.06-1.01, ptrend=0.05), and also among women with ER+ or PR+ status, HR 0.31 (0.10-0.98, ptrend=0.07), but this was not significant.

“Caan et al reported a trend toward decreased risk of death among tamoxifen users with intake of total isoflavones ≥6.3mg per day (median 26.7mg), HR 0.26 (0.06-1.01, ptrend=0.05), and also among women with ER+ or PR+ status, HR 0.31 (0.10-0.98, ptrend=0.07), but this was not significant [100].”

• cites [100] BJ Caan, 2011, Soy food consumption and breast cancer prognosis, Cancer Epidemiol Biomarkers Prev sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

In that prospective study, a similar association was found for ER+/PR+ patients and for those on anastrozole.

“A similar association was found for ER+/ PR+ patients and for those on anastrozole [106].”

• cites [106] X Kang, 2010, Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy, CMAJ sourceSupported

May combine two claims.

Eight of 12 (67%) studies examining high soy food or protein and six of seven (86%) studies examining high soy isoflavones reported inverse associations between soy and breast cancer risk.

“Eight of 12 (67%) studies examining high soy food or protein [45,46,61,64,72,77,78,81] and six of seven (86%) studies examining high soy isoflavones [42,43,45,75,77,81] reported inverse associations between soy and breast cancer risk.”

• cites [45] YY Zhu, 2011, Relationship between soy food intake and breast cancer in China, Asian Pac J Cancer PrevNot checked — no full text of the source
• cites [46] YA Cho, 2010, Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status, Eur J Clin Nutr sourceNot checked — no full text of the source
• cites [61] MK Kim, 2008, Dietary intake of soy protein and tofu in association with breast cancer risk based on a case-control study, Nutr Cancer sourceNot checked — no full text of the source
• cites [64] HP Lee, 1992, Risk factors for breast cancer by age and menopausal status: a case-control study in Singapore, Cancer Causes and Control sourceNot checked — no full text of the source
• cites [72] T Suzuki, 2008, Effect of soybean on breast cancer according to receptor status: a case-control study in Japan, Int J Cancer sourcePartly supported

  The Results (page not supplied) report an inverse association between soybean-product intake and overall breast cancer risk, so this paper supports its inclusion among the soy-food studies reporting an inverse association. The Assessment of soybean intake section describes measuring soy foods, not isoflavone intake. This paper also does not establish the citing sentence’s counts of eight of 12 and six of seven studies. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [77] AH Wu, 2002, Adolescent and adult soy intake and risk of breast cancer in Asian-Americans, Carcinogenesis sourceSupported
• cites [78] AH Wu, 2009, Dietary patterns and breast cancer risk in Asian American women, Am J Clin Nutr sourceSupported
• cites [81] C Zhang, 2010, Soy product and isoflavone intake and breast cancer risk defined by hormone receptor status, Cancer Sci sourceSupported
• cites [42] BA Boucher, 2013, Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk, Int J Cancer sourcePartly supported

  The section “Comparison with studies examining isoflavones from foods” says three meta-analyses suggest reduced breast cancer risk, including stronger inverse associations among high-isoflavone consumers. It also says individual study results are inconsistent. It does not report the claimed counts of 8 of 12 soy food or protein studies and 6 of 7 soy isoflavone studies, or their percentages. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [43] Q Wang, 2011, Soy isoflavones, CYP1A1, CYP1B1, and COMT polymorphisms, and breast cancer: a case-control study in southwestern China, DNA Cell Biol sourceNot checked — no full text of the source

The quote only partly states this claim.

Two additional prospective survival studies showed no significant effects.

“Two additional studies showed no significant effects [98,106].”

• cites [98] SM Boyapati, 2005, Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study, Breast Cancer Res Treat sourceNot checked — no full text of the source
• cites [106] X Kang, 2010, Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy, CMAJ sourcePartly supported

  The Menopausal status section reports no association between soy isoflavone intake and death, and no association with recurrence or death among premenopausal patients. But it also reports a significantly lower recurrence risk among postmenopausal patients with the highest intake, so describing this study as showing no significant effects is too broad. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Baseline mean number of hot flashes per day was 2.1 +/- 2.7 in the treatment group and 2.5 +/- 3.0 in the control group.

“Baseline mean number of hot flashes per day was 2.1 +/-2.7 for the treatment group and 2.5 +/-3.0 in the control group.”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourceCould not verify

  The Methods (Menopausal symptoms; page unavailable) say participants recorded daily hot flushes at baseline, and the Results (Hot flushes and menopausal symptoms; page unavailable) refer to Table 3. Searches for the claimed means and standard deviations did not find those figures in our copy, so the specific baseline comparison cannot be verified. (LLM, conf=0.72)

  Experimental — accuracy not yet measured

May combine two claims.

Powles reported adverse effects, most commonly breast abnormality, skin-related symptoms, and other minor adverse events, which were equally distributed between red clover and placebo groups.

“Powles reported adverse effects, which most commonly included breast abnormality, “skin related symptoms” (not described), and other minor adverse events, however these were equally distributed between red clover and placebo groups [166].”

• cites [166] TJ Powles, 2008, Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer, Menopause Int sourceCould not verify

  The retrieved passages contain bibliographic information but no results passage describing adverse effects. Searches for breast abnormalities, skin symptoms, adverse effects, and their distribution between the red-clover and placebo groups found no passage that addresses the claim. (LLM, conf=0.69)

  Experimental — accuracy not yet measured

May combine two claims.

Atkinson's RCT showed no significant changes in hot flash score (p=0.88) or mean number of daily hot flashes (p=0.41) when groups were compared.

“Results of the study by Atkinson showed no significant changes in hot flash score (p=0.88) or mean number of daily hot flashes (p=0.41) when groups were compared [165].”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourcePartly supported

  The Results section, “Hot flushes and menopausal symptoms” (page unavailable), reports no significant treatment-group effect on the number of hot flushes or the menopausal symptom score. It does not give the claimed p-values of 0.41 and 0.88 for those outcomes; the Methods section describes the score as covering 21 menopausal symptoms, not hot flashes alone. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The quote only partly states this claim.

Of nine RCTs assessing impact of soy on estrogen metabolism via urinary metabolites, five reports of six studies found no significant change in 2-hydroxyestrone, 16α-hydroxyestrone, or 2:16α hydroxyestrone ratio compared to control.

“Of these, five reports of six studies found no significant change in 2-hydroxyestrone, 16α-hydroxyestrone, or 2:16α hydroxyestrone ratio compared to the control group (p>0.05 for all) [148,149,156,161,164].”

• cites [148] G Maskarinec, 2002, The effects of an isoflavone intervention on the urinary excretion of hormone metabolites in premenopausal women, IARC Sci PublNot checked — no full text of the source
• cites [149] BD Brown, 2002, Types of dietary fat and soy minimally affect hormones and biomarkers associated with breast cancer risk in premenopausal women, Nutr Cancer sourceNot checked — no full text of the source
• cites [156] MC Martini, 1999, Effects of soy intake on sex hormone metabolism in premenopausal women, Nutr Cancer sourceNot checked — no full text of the source
• cites [161] G Maskarinec, 2012, Urinary estrogen metabolites in two soy trials with premenopausal women, Eur J Clin Nutr sourceSupported
• cites [164] Y Morimoto, 2012, Urinary estrogen metabolites during a randomized soy trial, Nutr Cancer sourcePartly supported

  The Results report no change in 2-hydroxyestrone (p=0.40) and a nonsignificant decrease in 16α-hydroxyestrone (p=0.21). But they report a marginally significant increase in the 2:16α ratio (p=0.05), not p>0.05 for all three outcomes. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

In 5042 breast cancer survivors, roughly half of whom were on tamoxifen, soy protein intake (>15.31 mg/d) was protective against recurrence and death, with HR for recurrence 0.66 (0.52-0.84).

“Shu et al examined 5042 breast cancer survivors, roughly half of whom were on tamoxifen (n=2262), and found that both soy protein intake (>15.31mg/d) and total isoflavone intake (>62.68mg/d) were protective against recurrence and death, HR recurrence 0.66 (0.52-0.84) for protein, and HR 0.74 (0.59-0.95) for isoflavones [112].”

• cites [112] XO Shu, 2009, Soy food intake and breast cancer survival, JAMA sourcePartly supported

  The Results report lower mortality and recurrence with higher soy protein intake, including the stated recurrence HR of 0.66 (95% CI 0.52–0.84); they also report the stated isoflavone recurrence HR of 0.74 (0.59–0.95). The Methods say 5,042 women enrolled but 5,033 were analyzed. The cited copy does not substantiate the quoted >15.31 mg/day protein cutoff, and the Discussion describes soy protein intake in grams per day. These are observational associations, not proof that soy intake was protective. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

The WHEL cohort had relatively low soy isoflavone intake (≥6.3 mg total isoflavones) and yielded null results, with an HR for recurrence among tamoxifen users of 0.59 (0.27-1.29).

“Of the cohort studies, the WHEL cohort exhibited relatively low soy isoflavone intake (≥6.3mg total isoflavones) and yielded null results: HR for recurrence among tamoxifen users was 0.59 (0.27-1.29) [100].”

• cites [100] BJ Caan, 2011, Soy food consumption and breast cancer prognosis, Cancer Epidemiol Biomarkers Prev sourcePartly supported

  The Discussion describes mean soy intake in WHEL as much lower than in a Chinese cohort, and Data Analyses identifies 6.3–86.9 mg/day as the highest intake category. The Results report no significant association with a second breast cancer event among women who had ever used tamoxifen. The exact HR of 0.59 and 95% CI of 0.27–1.29 are not stated in the available passages, so those figures cannot be verified from our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Atkinson reported no significant change in FSH: FSH decreased 4.2 IU/L in the red clover group compared with a decrease of 2.9 in the placebo group, p=0.83.

“FSH decreased 4.2 IU/L in the red clover group compared to a decrease of 2.9 in the placebo group, p=0.83;”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourcePartly supported

  The Results section on oestradiol and gonadotrophins states that treatment group had no significant effect on change in FSH. Our copy does not provide the claimed overall decreases of 4.2 and 2.9 IU/L or P = 0.83; the Results refer to Table 2 but give only genotype-specific FSH changes in the available passage. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

May combine two claims.

In studies among healthy women, there were no significant changes compared to baseline in endometrial thickness, rates of normal mammogram results, menstrual cycle length, urinary excretion of estrogen, or ratio of urinary estrogen metabolites 2:16 OH-estrone.

“In studies conducted among healthy women, there were no significant changes compared to baseline in endometrial thickness [118]; rates of normal mammogram results [118]; menstrual cycle length [120-122]; or urinary excretion of estrogen [123] or the ratio of urinary estrogen metabolites 2:16 OH-estrone (E1) [123,124].”

• cites [118] S Palacios, 2010, Long-term endometrial and breast safety of a specific, standardized soy extract, Climacteric sourceNot checked — no full text of the source
• cites [120] AH Wu, 2000, Effects of soy foods on ovarian function in premenopausal women, Br J Cancer sourceSupported
• cites [121] LJ Lu, 2000, Decreased ovarian hormones during a soya diet: implications for breast cancer prevention, Cancer ResNot checked — no full text of the source
• cites [122] LJ Lu, 1996, Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction, Cancer Epidemiol Biomarkers PrevNot checked — no full text of the source
• cites [123] G Maskarinec, 2005, Urinary sex steroid excretion levels during a soy intervention among young girls: a pilot study, Nutr Cancer sourcePartly supported

  The Results report no statistically significant change in total urinary estrogen excretion during the soy intervention (P = 0.87). However, the participants were girls aged 8–14, not adult women. The Materials and Methods list 2- and 16α-hydroxyestrone as measured metabolites, but the Results do not report a change in their ratio. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [124] LA Cohen, 2007, Soy isoflavone intake and estrogen excretion patterns in young women: effect of probiotic administration, In VivoNot checked — no full text of the source

May combine two claims.

In Atkinson's study, hot flashes were a secondary endpoint and baseline menopausal symptom severity was already low; menopausal symptoms were not present in all subjects.

“Nonetheless, it should be noted that this was a secondary endpoint, and that this study included women in whom the severity of menopausal symptoms was already low at baseline; menopausal symptoms were not present in all subjects.”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourceSupported

May combine two claims.

Two of five RCTs assessing menstrual cycle length reported significant increases of 1.8 to 3.5 days in cycle length associated with soy consumption compared to control; remaining studies found no effects.

“Two of five studies assessing menstrual cycle length reported significant increases of between 1.8 to 3.5 days in cycle length associated with soy consumption compared to control subjects [149,150]; the remaining studies found no effects [147,156,158].”

• cites [149] BD Brown, 2002, Types of dietary fat and soy minimally affect hormones and biomarkers associated with breast cancer risk in premenopausal women, Nutr Cancer sourceNot checked — no full text of the source
• cites [150] NB Kumar, 2002, The specific role of isoflavones on estrogen metabolism in premenopausal women, Cancer sourceSupported
• cites [147] G Maskarinec, 2002, A randomized isoflavone intervention among premenopausal women, Cancer Epidemiology, Biomarkers and PreventionNot checked — no full text of the source
• cites [156] MC Martini, 1999, Effects of soy intake on sex hormone metabolism in premenopausal women, Nutr Cancer sourceNot checked — no full text of the source
• cites [158] C Nagata, 1998, Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women, J Natl Cancer Inst sourceNot checked — no full text of the source

May combine two claims.

A total of 18 RCTs assessed circulating estrogen levels; 15 of 18 found no significant impact from soy compared to control.

“A total of 18 RCTs assessed circulating estrogens levels (E1, E2, and/ or E3) Fifteen of 18 studies found no significant impact from soy compared to the control group (p>0.05) [129,132,133,138,140,143,145,147,149,150,155,156,158,160,163].”

• cites [129] E Nikander, 2003, A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients, Obstet Gynecol sourceNot checked — no full text of the source
• cites [132] FM Steinberg, 2011, Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women, Am J Clin Nutr sourceNot checked — no full text of the source
• cites [133] JM McLaughlin, 2011, Effects of tomato- and soy-rich diets on the igf-I hormonal network: a crossover study of postmenopausal women at high risk for breast cancer, Cancer Prev Res (Phila) sourcePartly supported

  The Methods (Measurement; page unavailable) list estradiol as a measured endpoint, and the Results (Soy Arm; page unavailable) identify significant changes in other biomarkers but not estradiol. This supports treating the paper as a soy-intervention study that assessed a circulating estrogen, but it does not establish the claim's count of 18 RCTs or 15 null findings. The study compared measurements before and after its soy arm rather than reporting a soy-versus-control-group result. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [138] EA Pop, 2008, Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: A phase I clinical trial, Menopause sourceSupported
• cites [140] AH Wu, 2005, A controlled 2-mo dietary fat reduction and soy food supplementation study in postmenopausal women, Am J Clin Nutr sourceNot checked — no full text of the source
• cites [143] A Zittermann, 2004, Short-term effects of high soy supplementation on sex hormones, bone markers, and lipid parameters in young female adults, Eur J Nutr sourceNot checked — no full text of the source
• cites [145] G Maskarinec, 2004, Effects of a 2-year randomized soy intervention on sex hormone levels in premenopausal women, Cancer Epidemiol Biomarkers Prev sourceNot checked — no full text of the source
• cites [147] G Maskarinec, 2002, A randomized isoflavone intervention among premenopausal women, Cancer Epidemiology, Biomarkers and PreventionNot checked — no full text of the source
• cites [149] BD Brown, 2002, Types of dietary fat and soy minimally affect hormones and biomarkers associated with breast cancer risk in premenopausal women, Nutr Cancer sourceNot checked — no full text of the source
• cites [150] NB Kumar, 2002, The specific role of isoflavones on estrogen metabolism in premenopausal women, Cancer sourceSupported

May combine two claims.

At 12 months, the red clover group had a decrease of -0.8 +/- 2.1 and the control group a decrease of -1.0 +/- 1.8 (p=0.41), which was not significant.

“There was a comparable decrease of -0.8 +/-2.1 at 12 months for the red clover group and -1.0 +/-1.8 for the control group (p=0.41), which however was not significant.”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourcePartly supported

  The Results section on hot flushes and menopausal symptoms (page unavailable) reports no significant treatment-group effect, and the Discussion says symptoms decreased to a similar extent in both groups. Our copy does not show the claimed changes of −0.8 ± 2.1 and −1.0 ± 1.8 or P = 0.41, so those figures cannot be verified. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

The most common adverse event associated with soy consumption was mild to moderate gastrointestinal discomfort, usually occurring with comparable frequency in soy and placebo groups.

“The most common adverse event associated with soy consumption was mild to moderate gastrointestinal discomfort, but this usually occurred with comparable frequency in both the soy and the placebo groups [128,130,131,136,142,147,150]; only in one study was there considerable difference in the frequency of GI upset, 47% in the soy group compared to 22% in the control group [130].”

• cites [128] CA MacGregor, 2005, A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer, Eur J Cancer sourceNot checked — no full text of the source
• cites [130] CL Van Patten, 2002, Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, Controlled Clinical Trials - Journal of Clinical Oncology sourceNot checked — no full text of the source
• cites [131] SK Quella, 2000, Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial, J Clin Oncol sourceNot checked — no full text of the source
• cites [136] H Marini, 2008, Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study, J Clin Endocrinol Metab sourceNot checked — no full text of the source
• cites [142] E Nikander, 2004, Effects of phytoestrogens on bone turnover in postmenopausal women with a history of breast cancer, Journal of Clinical Endocrinology and Metabolism sourceNot checked — no full text of the source
• cites [147] G Maskarinec, 2002, A randomized isoflavone intervention among premenopausal women, Cancer Epidemiology, Biomarkers and PreventionNot checked — no full text of the source
• cites [150] NB Kumar, 2002, The specific role of isoflavones on estrogen metabolism in premenopausal women, Cancer sourcePartly supported

  The Results (page unavailable) report that product intolerance involving bloating or nausea led to withdrawal of two women in the soy group and two in the placebo group. That supports comparable frequency for those withdrawals, but the paper does not establish that gastrointestinal discomfort was the most common adverse event, grade it as mild to moderate, or show comparable frequency for all gastrointestinal symptoms. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

In 5042 breast cancer survivors, roughly half of whom were on tamoxifen, total isoflavone intake (>62.68 mg/d) was protective against recurrence and death, with HR for recurrence 0.74 (0.59-0.95).

“Shu et al examined 5042 breast cancer survivors, roughly half of whom were on tamoxifen (n=2262), and found that both soy protein intake (>15.31mg/d) and total isoflavone intake (>62.68mg/d) were protective against recurrence and death, HR recurrence 0.66 (0.52-0.84) for protein, and HR 0.74 (0.59-0.95) for isoflavones [112].”

• cites [112] XO Shu, 2009, Soy food intake and breast cancer survival, JAMA sourcePartly supported

  The Results report lower mortality and recurrence with higher soy isoflavone intake, including a recurrence HR of 0.74 (95% CI 0.59–0.95). The Study population section says 5,042 women participated, but 5,033 were analyzed. The passages do not establish the stated >62.68 mg/day cutoff or the 2,262 tamoxifen-user count, and the reported association does not establish that isoflavones were protective in a causal sense. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Atkinson reported no significant change in tyrosine kinase: tyrosine kinase increased 1.62 units of activity/μg protein in the red clover group compared with an increase of 0.90 in the placebo group, p=0.16.

“and tyrosine kinase increased 1.62 units of activity/ µg protein in the red clover group compared to an increase of 0.90 in the placebo group, p=0.16 [165].”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourceSupported

May combine two claims.

One RCT found consumption of an isoflavone supplement (235mg daily) for six months had no effect on Ki-67 labeling index compared to placebo, although there was a significant decrease in both treatment and placebo groups compared to baseline.

“On the other hand, a recent study found that consumption of an isoflavone supplement (235mg daily) for six months had no effect on Ki-67 labeling index compared to placebo, although there was a significant decrease in both treatment and placebo groups compared to baseline [160].”

• cites [160] SA Khan, 2012, Soy isoflavone supplementation for breast cancer risk reduction: a randomized phase II trial. Cancer, Prev Res (Phila Pa) sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

May combine two claims.

Atkinson reported no significant change in LH: LH decreased 4.0 IU/L in the red clover group compared with a decrease of 4.2 IU/L in the placebo group, p=0.71.

“LH decreased 4.0 IU/L in the red clover group compared to a decrease of 4.2 IU/L in the placebo group, p=0.71;”

• cites [165] C Atkinson, 2004, Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165, Breast Cancer Research sourcePartly supported

  The Results section on luteinizing hormone reports no significant treatment-group effect on the change in LH. Our copy does not give the claimed decreases of 4.0 and 4.2 IU/L or P = 0.71; the Results refer to Table 2, but those figures are not present in the available passages. The Methods section says LH changes were assessed only in postmenopausal women. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

Preclinical evidence shows that under high estrogen concentrations similar to premenopausal levels, soy isoflavones act as ER antagonists, while under low estrogen concentrations comparable to postmenopausal levels, they are ER agonists.

“Secondly, preclinical evidence has shown that under conditions of high estrogen concentration similar to premenopausal levels, soy isoflavones act as ER antagonists, while under conditions of low estrogen comparable to postmenopausal levels, they are ER agonists [12,181,182].”

• cites [12] M Velders, 2010, Estradiol and genistein antagonize the ovariectomy effects on skeletal muscle myosin heavy chain expression via ER-beta mediated pathways, J Steroid Biochem Mol Biol sourceNot checked — no full text of the source
• cites [181] YH Ju, 2006, Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations, Carcinogenesis sourceNot checked — no full text of the source
• cites [182] W Qin, 2009, Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women, Nutr Cancer sourcePartly supported

  The Discussion (page not provided) reports preliminary evidence of an antiestrogenic effect in healthy premenopausal women, supporting one part of the claim. The paper does not establish that ER activity switches with estrogen concentration or that soy isoflavones act as ER agonists under postmenopausal-level estrogen; its discussion of differing effects concerns isoflavone dose and circulating genistein levels, not estrogen levels. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Soy consumption may protect against the development of breast cancer, and less so against breast cancer recurrence and mortality, although this is based on observational data only.

“Our review suggests that on the contrary, soy consumption may protect against the development of breast cancer [46,75,109,117], and less so, breast cancer recurrence and mortality [106,112], although this is based on observational data only.”

• cites [46] YA Cho, 2010, Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status, Eur J Clin Nutr sourceNot checked — no full text of the source
• cites [75] Q Wang, 2010, Polymorphic catechol-O-methyltransferase gene, soy isoflavone intake and breast cancer in postmenopausal women: a case-control study, Chin J Cancer sourceNot checked — no full text of the source
• cites [109] SA Lee, 2009, Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study, Am J Clin Nutr sourcePartly supported

  The Results reported in the Abstract and the Discussion’s summary find an inverse association between soy intake and new breast cancer cases in premenopausal Chinese women. The paper found no significant association for postmenopausal breast cancer, so it does not support the claim without that population qualifier. The separate citations following recurrence and mortality do not attribute those outcomes to this paper. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [117] M Iwasaki, 2008, Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group, J Clin Oncol sourceSupported
• cites [106] X Kang, 2010, Effect of soy isoflavones on breast cancer recurrence and death for patients receiving adjuvant endocrine therapy, CMAJ sourcePartly supported

  The Menopausal status section reports an observational association between higher soy isoflavone intake and lower recurrence risk in postmenopausal patients receiving endocrine therapy. It reports no association with death, including breast-cancer mortality, and no association with recurrence among premenopausal patients. This source is cited for recurrence and mortality, not for the separate claim about breast cancer development. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [112] XO Shu, 2009, Soy food intake and breast cancer survival, JAMA sourceSupported

• AssumptionRests on an assumption: The observational studies' measures of soy intake accurately reflect long-term soy exposure relevant to breast cancer risk.
• AssumptionRests on an assumption: The findings from the included studies are sufficiently representative of women with breast cancer or at risk that they can be generalized to most women.

May combine two claims.

Some preliminary evidence indicates that isoflavones may have synergistic effects with tamoxifen in cancer models and may reduce the development of tamoxifen resistance.

“Some preliminary evidence indicates that isoflavones may have synergistic effects with tamoxifen in cancer models and may reduce the development of tamoxifen resistance [185,186].”

• cites [185] Z Mai, 2007, Genistein sensitizes inhibitory effect of tamoxifen on the growth of estrogen receptor-positive and HER2-overexpressing human breast cancer cells, Mol Carcinog sourceNot checked — no full text of the source
• cites [186] Z Mai, 2007, Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice, Carcinogenesis sourcePartly supported

  The Discussion reports additive-to-synergistic inhibition of MCF-7 tumor growth in mice when tamoxifen was combined with genistein or soy phytochemical concentrate. It does not report that isoflavones reduce the development of tamoxifen resistance; the resistance references concern other treatments or studies. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues.

“Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues.”

• AssumptionRests on an assumption: Circulating estradiol and effects on estrogen-responsive tissues are valid surrogate endpoints for predicting breast cancer risk.

May combine two claims.

Evidence on red clover is limited, but existing studies suggest it may not possess breast cancer-promoting effects.

“Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects.”

The quote only partly states this claim.

There were no case-control studies showing significantly increased risk of breast cancer associated with soy intake.

“There were no studies showing significantly increased risk of breast cancer associated with soy intake.”

The quote only partly states this claim.

There were no prospective cohort studies indicating a higher risk of breast cancer associated with soy consumption.

“There were no studies indicating a higher risk of breast cancer associated with soy consumption.”

May combine two claims.

On subgroup analysis, there was no clear difference in effect based on type of soy exposure, study quality, measure of exposure, or menopausal status.

“On subgroup analysis, there was no clear difference in effect based on the type of soy exposure (food / protein, or isoflavones), or according to study quality (NOS score), the measure of exposure (recall or measurement of blood or urinary isoflavone levels), or menopausal status (Figures S1-S2 ).”

May combine two claims.

Two of nine (22%) studies examining low-medium soy food/protein intake and zero of three studies examining low-medium soy isoflavone intake found inverse associations.

“On the other hand, two of nine (22%) and zero of three studies respectively found inverse associations with low-medium intake [44,71].”

• cites [44] AK Zaineddin, 2012, The association between dietary lignans, phytoestrogen-rich foods, and fiber intake and postmenopausal breast cancer risk: a German case-control study, Nutr Cancer sourceNot checked — no full text of the source
• cites [71] XO Shu, 2001, Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women, Cancer Epidemiol Biomarkers PrevNot checked — no full text of the source

May combine two claims.

Grace et al reported a small but significant increase in risk of breast cancer associated with higher serum daidzein and serum and urinary equol levels, indicating 30-45% increased odds with a doubling of daidzein and equol levels.

“Grace et al reported a small but significant increase in risk of breast cancer associated with higher serum daidzein and serum and urinary equol levels; this was expressed as a log2 odds ratio (associated with doubling of exposure) and as a different measure was not included in the forest plots [88]. Nonetheless, these findings indicated a 30-45% increased odds of breast cancer with a doubling of”

• cites [88] PB Grace, 2004, Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutrition-norfolk, Cancer Epidemiol Biomarkers Prev sourceNot checked — no full text of the source

May combine two claims.

In one RCT, vaginal spotting was reported in four subjects in the soy group compared to one in the placebo group, but statistical significance was not reported because of low numbers.

“In one RCT, vaginal spotting was reported in four subjects in the soy group compared to one in the placebo group, but with such low numbers, the statistical significance of this finding was not reported [130].”

• cites [130] CL Van Patten, 2002, Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, Controlled Clinical Trials - Journal of Clinical Oncology sourceNot checked — no full text of the source

May combine two claims.

One RCT found no change in BRCA 1 and 2 mRNA level due to soy consumption, but there was a decrease over time in the placebo group, yielding a significant difference between groups (p<0.001).

“One study found no change in BRCA 1 and 2 mRNA level due to soy consumption, however there was a decrease over time in the placebo group, yielding a significant difference between groups (p<0.001) [136].”

• cites [136] H Marini, 2008, Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study, J Clin Endocrinol Metab sourceNot checked — no full text of the source

May combine two claims.

With respect to nipple aspirate volume, one study showed no change while one found a significant increase among premenopausal women only, from 16 to 36 μL.

“With respect to nipple aspirate volume (NAV), a marker of breast tissue proliferative activity, one study showed no change [126] while one study found a significant increase in NAV among premenopausal women only, from 16 to 36 µL [125].”

• cites [126] G Maskarinec, 2008, The relation of soy intake and isoflavone levels in nipple aspirate fluid, Eur J Cancer Prev sourceNot checked — no full text of the source
• cites [125] NL Petrakis, 1996, Stimulatory influence of soy protein isolate on breast secretion in pre- and postmenopausal women, Cancer Epidemiol Biomarkers PrevNot checked — no full text of the source

May combine two claims.

Case-control studies were much more likely to report significant protective associations between soy intake and risk of breast cancer, while prospective studies were less likely to do so.

“As shown in Figures 2 and 3 , case control studies were much more likely to report significant protective associations between soy intake and risk of breast cancer, while prospective studies were less likely to do so.”

May combine two claims.

RCTs noted some improvements in hot flashes over time, but not in comparison to placebo.

“RCTs noted some improvements over time, but not in comparison to placebo [127-131].”

• cites [127] WC Dooley, 2006, Internet based double-blind cross-over clinical trial to test efficacy of high dose isoflavone soy in controlling breast cancer survivor hot flashes, Journal of Clinical Oncology sourceNot checked — no full text of the source
• cites [128] CA MacGregor, 2005, A randomised double-blind controlled trial of oral soy supplements versus placebo for treatment of menopausal symptoms in patients with early breast cancer, Eur J Cancer sourceNot checked — no full text of the source
• cites [129] E Nikander, 2003, A randomized placebo-controlled crossover trial with phytoestrogens in treatment of menopause in breast cancer patients, Obstet Gynecol sourceNot checked — no full text of the source
• cites [130] CL Van Patten, 2002, Effect of soy phytoestrogens on hot flashes in postmenopausal women with breast cancer: a randomized, Controlled Clinical Trials - Journal of Clinical Oncology sourceNot checked — no full text of the source
• cites [131] SK Quella, 2000, Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: A North Central Cancer Treatment Group Trial, J Clin Oncol sourceNot checked — no full text of the source

May combine two claims.

The review found variation according to geographical locale: studies conducted in Asian countries more often reported chemopreventive effects compared to studies in Western countries, which more often reported null results.

“However we did find variation according to geographical locale; studies conducted in Asian countries more often reported chemopreventive effects compared to studies in Western countries, which more often reported null results.”

May combine two claims.

The review found no effects on circulating estradiol and no measurable effects on estrogen-sensitive target tissues, such as breast tissue density and endometrium.

“We found no effects on circulating estradiol, and no measurable effects on estrogen-sensitive target tissues, such as breast tissue (density) and endometrium.”

May combine two claims.

Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality.

“Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality.”

May combine two claims.

Soy intake consistent with a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence.

“Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence.”

May combine two claims.

CC and CT genotypes may be associated with a small reduction in risk of breast cancer compared to TT: CC vs TT OR 0.92 (95% CI 0.86-0.99), and CC/CT vs TT OR 0.95 (95% CI 0.89-1.00).

“For instance, CC and CT genotypes may be associated with a small reduction in risk of breast cancer compared to TT: CC vs. TT: OR 0.92, 95%CI 0.86-0.99, and CC/CT vs. TT: OR 0.95, 95%CI 0.89-1.00 [167].”

• cites [167] N Li, 2010, Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis, Breast Cancer Res Treat sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

ESR1 codes for estrogen receptor α, and variations may be associated with risk of breast cancer.

“ESR1 codes for the estrogen receptor α, and variations may be associated with risk of breast cancer [167].”

• cites [167] N Li, 2010, Potentially functional polymorphisms in ESR1 and breast cancer risk: a meta-analysis, Breast Cancer Res Treat sourceNot checked — no full text of the source

May combine two claims.

RCTs were assessed as having moderate risk of bias, with inadequate reporting of random sequence generation and allocation concealment in 18 and 32 of 43 unique RCTs, respectively.

“RCTs were assessed as having a moderate risk of bias, with inadequate reporting of random sequence generation and allocation concealment (selection bias) in 18 and 32 of 43 unique RCTs, respectively.”

May combine two claims.

The majority of RCTs showed low risk of performance bias, detection bias, attrition bias, and reporting bias; description of blinding of participants, blinding of outcome assessment, complete outcome data and reporting was adequate in over 88% of the studies.

“The majority of RCTs showed low risk of performance bias, detection bias, attrition bias, and reporting bias; description of blinding of participants, blinding of outcome assessment, complete outcome data and reporting was adequate in over 88% of the studies.”

Probably not a substantial claim: may not pass S4 (based).

RCTs of under 2 years duration are unlikely to reveal any serious adverse effects in breast cancer survivors, including possible interactions between soy and tamoxifen.

“This is a particularly important shortcoming because RCTs of under 2 years duration are unlikely to reveal any serious adverse effects in breast cancer survivors, including possible interactions between soy and tamoxifen.”

May combine two claims.

According to Imhof, typical in vivo estrogen levels range from 50-400 pM, with even menopausal estrogen levels exceeding 20 pM, the concentration of genistein achieved through supplementation.

“According to Imhof, typical in vivo estrogen levels range from 50–400 pM, with even menopausal estrogen levels exceeding 20 pM, the concentration of genistein achieved through supplementation [18].”

• cites [18] M Imhof, 2008, Effects of soy isoflavones on 17beta-estradiol-induced proliferation of MCF-7 breast cancer cells, Toxicol In Vitro sourceNot checked — no full text of the source

May combine two claims.

The review's findings are generally in agreement with the American Cancer Society, suggesting that moderate amounts of soy intake (up to 3 servings per day) are likely safe for consumption by women with breast cancer.

“Our findings are generally in agreement with those of the American Cancer Society, suggesting that moderate amounts of soy intake (up to 3 servings per day) is likely safe for consumption by women with breast cancer [190].”

• cites [190] C Doyle, 2006, Nutrition and physical activity during and after cancer treatment: An American Cancer Society guide for informed choices, CA Cancer J Clin sourceNot checked — no full text of the source

• AssumptionRests on an assumption: The findings from the included studies are sufficiently representative of women with breast cancer or at risk that they can be generalized to most women.

May combine two claims.

Tamoxifen acts primarily through ERα while soy is preferential toward ERβ, which theoretically suggests minimal risk of interaction based on competitive receptor binding, although this has not been tested clinically.

“Tamoxifen acts primarily through the ERα while soy is preferential toward ERß, which theoretically suggests minimal risk of interaction based on competitive receptor binding, however this has not been tested clinically [176,178].”

• cites [176] KF Koehler, 2005, Reflections on the discovery and significance of estrogen receptor beta, Endocr Rev sourceNot checked — no full text of the source
• cites [178] A Clemente, 2011, Bowman-birk inhibitors from legumes and human gastrointestinal health: current status and perspectives, Curr Protein Pept Sci sourceNot checked — no full text of the source

May combine two claims.

Soy does not appear to influence levels of circulating estrogen or exert estrogen-like effects at target tissues.

“Soy does not appear to influence levels of circulating estrogen or exert estrogen-like effects at target tissues.”

May combine two claims.

In a study of soy and MCF-7 breast cancer cell growth, Imhof et al observed "minor proliferation enhancing effects" that occurred "only at unphysiologically low estrogen levels".

“In a study of soy and MCF-7 breast cancer cell growth as assessed in the presence and absence of estradiol, Imhof et al observed “minor proliferation enhancing effects” [18] that occurred “only at unphysiologically low estrogen levels” [18].”

• cites [18] M Imhof, 2008, Effects of soy isoflavones on 17beta-estradiol-induced proliferation of MCF-7 breast cancer cells, Toxicol In Vitro sourceNot checked — no full text of the source

May combine two claims.

Hooper found that soy did not significantly affect estradiol, estrone, or sex hormone binding globulin, although among pre-menopausal women there was a significant 20% decrease in LH and FSH (p=0.01, 0.5 respectively).

“Hooper found that soy did not significantly affect estradiol, estrone, or sex hormone binding globulin (SHBG), although amongst pre-menopausal women there was a significant 20% decrease in LH and FSH (p=0.01, 0.5 respectively) [31].”

• cites [31] JM Wong, 2012, Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods, Am J Clin Nutr sourceNot checked — no full text of the source

May combine two claims.

Moderate soy consumption appears to be safe and possibly beneficial for most women.

“In the meantime, since the overall effect of soy, if any, appears to be protective for both breast cancer incidence and recurrence, moderate soy consumption appears to be safe and possibly beneficial for most women.”

• AssumptionRests on an assumption: The absence of observed harm from soy in the reviewed studies is sufficient to conclude that moderate soy consumption is safe for most women.

May combine two claims.

In the breast, ERβ is found in ductal and lobular epithelial cells as well as stromal cells, while ERα is found only in epithelial cells and not stroma.

“In the breast, ERß is found in ductal and lobular epithelial cells as well as stromal cells, while ERα is found only in epithelial cells and not stroma of the breast [177].”

• cites [177] JLY Chen, 2011, Natural products targeting telomere maintenance, MedChemComm sourceNot checked — no full text of the source

May combine two claims.

The in vitro receptor binding activity of genistein, daidzein, equol, and their metabolites is approximately 3% or less that of estradiol for ERα, and 18% or less for ERβ.

“The in vitro receptor binding activity of genistein, daidzein, equol, and their metabolites is approximately 3% or less that of estradiol for ERα, and 18% or less for ERß [187]”

• cites [187] A Boumendjel, 2011, Targeting the multidrug ABCG2 transporter with flavonoidic inhibitors: In Vitro optimization and in vivo validation, Curr Med Chem sourceNot checked — no full text of the source

May combine two claims.

In post-menopausal women there were no significant effects on any hormone including estradiol and estrone, with a small nonsignificant 14% increase in estradiol based on 21 studies (p=0.07) and a nonsignificant decrease in estrone.

“In post-menopausal women there were no significant effects on any hormone including estradiol and estrone, with a small nonsignificant 14% increase in estradiol based on 21 studies (p=0.07) and a nonsignificant decrease in estrone.”

• cites [31] JM Wong, 2012, Equol status and blood lipid profile in hyperlipidemia after consumption of diets containing soy foods, Am J Clin Nutr sourceNot checked — no full text of the source

May combine two claims.

The traditional Japanese diet contains between 6-11 g of soy protein and 25-50 mg isoflavones; top percentiles of soy intake in Asian studies consume as much as 20 g soy protein or 100 mg isoflavones per day, while the cut-off for top quartiles of intake among Western populations is in the range of a few hundred micrograms per day.

“The traditional Japanese diet contains between 6-11g of soy protein and 25-50mg isoflavones; top percentiles of soy intake in Asian studies consume as much as 20g soy protein or 100mg isoflavones per day [188], while the cut off for the top quartiles of intake among Western populations is in the range of a few hundred micrograms (mcg) per day [52,74].”

• cites [188] M Messina, 2006, Estimated Asian adult soy protein and isoflavone intakes, Nutr Cancer sourceNot checked — no full text of the source
• cites [52] P Mangtani, 2004, Phyto-oestrogen intake and breast cancer risk in South Asian women in England: findings from a population-based case-control study, Cancer Causes Control sourceNot checked — no full text of the source
• cites [74] MS Touillaud, 2005, Effect of dietary intake of phytoestrogens on estrogen receptor status in premenopausal women with breast cancer, Nutr Cancer sourceNot checked — no full text of the source

May combine two claims.

ERβ appears to be associated with antiproliferative, anticarcinogenic effects, while ERα is thought to promote carcinogenesis and is the form measured clinically in the treatment of breast cancer patients.

“This is important because ERß appears to be associated with antiproliferative, anticarcinogenic effects, while ERα is thought to promote carcinogenesis, and is the form measured clinically in the treatment of breast cancer patients [176,177].”

• cites [176] KF Koehler, 2005, Reflections on the discovery and significance of estrogen receptor beta, Endocr Rev sourceNot checked — no full text of the source
• cites [177] JLY Chen, 2011, Natural products targeting telomere maintenance, MedChemComm sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

ERα is the receptor used to classify ER-positive breast cancer and the one through which tamoxifen exerts its antiproliferative effects.

“Moreover, ERα is the receptor used to classify ER positive breast cancer, and the one through which tamoxifen exerts its antiproliferative effects [176,178].”

• cites [176] KF Koehler, 2005, Reflections on the discovery and significance of estrogen receptor beta, Endocr Rev sourceNot checked — no full text of the source
• cites [178] A Clemente, 2011, Bowman-birk inhibitors from legumes and human gastrointestinal health: current status and perspectives, Curr Protein Pept Sci sourceNot checked — no full text of the source

May combine two claims.

Observational data suggest that higher soy intake, consistent with a traditional Japanese diet, may be protective against the development of breast cancer as well as breast cancer recurrence and mortality, although clinical studies are needed to confirm this relationship.

“Observational data suggest that higher soy intake, consistent with that of a traditional Japanese diet, may be protective against the development of breast cancer as well as breast cancer recurrence and mortality, although there is a need for clinical studies to confirm this relationship.”

• AssumptionRests on an assumption: The observational studies' measures of soy intake accurately reflect long-term soy exposure relevant to breast cancer risk.
• AssumptionRests on an assumption: The findings from the included studies are sufficiently representative of women with breast cancer or at risk that they can be generalized to most women.