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Cited by 436Phytoestrogen effects and researchNutritional Studies and DietCancer Risks and Factors

Soy food intake and breast cancer survival

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Shu, Xiao Ou·2009·JAMA
DOI 10.1001/jama.2009.1783PMC PMC2874068
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Abstract

CONTEXT: Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer. However, the estrogen-like effect of isoflavones and the potential interaction between isoflavones and tamoxifen have led to concern about soy food consumption among breast cancer patients. OBJECTIVE: To evaluate the association of soy food intake after diagnosis of breast cancer with total mortality and cancer recurrence. DESIGN, SETTING, AND PARTICIPANTS: The Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5042 female breast cancer survivors in China. Women aged 20 to 75 years with diagnoses between March 2002 and April 2006 were recruited and followed up through June 2009. Information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression was collected at approximately 6 months after cancer diagnosis and was reassessed at 3 follow-up interviews conducted at 18, 36, and 60 months after diagnosis. Annual record linkage with the Shanghai Vital Statistics Registry database was carried out to obtain survival information for participants who were lost to follow-up. Medical charts were reviewed to verify disease and treatment information. MAIN OUTCOME MEASURES: Total mortality and breast cancer recurrence or breast cancer-related deaths. Cox regression analysis was carried out with adjustment for known clinical predictors and other lifestyle factors. Soy food intake was treated as a time-dependent variable. RESULTS: During the median follow-up of 3.9 years (range, 0.5-6.2 years), 444 deaths and 534 recurrences or breast cancer-related deaths were documented in 5033 surgically treated breast cancer patients. Soy food intake, as measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. The hazard ratio associated with the highest quartile of soy protein intake was 0.71 (95% confidence interval [CI], 0.54-0.92) for total mortality and 0.68 (95% CI, 0.54-0.87) for recurrence compared with the lowest quartile of intake. The multivariate-adjusted 4-year mortality rates were 10.3% and 7.4%, and the 4-year recurrence rates were 11.2% and 8.0%, respectively, for women in the lowest and highest quartiles of soy protein intake. The inverse association was evident among women with either estrogen receptor-positive or -negative breast cancer and was present in both users and nonusers of tamoxifen. CONCLUSION: Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence.

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  • Four cohort studies and three RCTs reported no significant differences in treatment outcomes or rates of adverse effects associated with soy use among women receiving tamoxifen therapy.

    “Four cohort studies [100,103,106,112] and three RCTs [128,130,131] reported no significant differences with respect to treatment outcomes or rates of adverse effects associated with use of soy among women who were receiving tamoxifen therapy.”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [112]

    The Results (page unavailable) report that recurrence estimates for women using tamoxifen were not statistically significant and that the interaction between soy intake and tamoxifen use was not significant. But the paper describes lower mortality and recurrence with higher soy intake regardless of tamoxifen use, rather than simply reporting no difference in outcomes. It does not report rates of adverse effects. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • 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].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [112]

    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

  • When analyzed by receptor status, the associations between soy intake and recurrence remained significant only among women with ER+ status.

    “When analyzed by receptor status, these associations remained significant only among women with ER+ status [112].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [112]

    The Results report that the association between soy intake and recurrence was observed in both ER-positive and ER-negative women. The indexed passages do not give receptor-stratified significance results, so they do not establish the claim that it remained statistically significant only in ER-positive women. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • 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].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [112]

    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

  • Of four prospective studies reporting risk for the overall study population, one (25%) found significantly decreased risk of breast cancer recurrence or longer disease-free survival associated with higher soy intake.

    “Four studies reported risk for the overall study population (Figure S4 ), of which one (25%) found significantly decreased risk of breast cancer recurrence or longer disease-free survival (defined as combined relapse or death related to breast cancer) associated with higher soy intake [112].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [112]

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Research works printed but not linked: 35

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Authors
Shu, X. O.
Affiliations
Vanderbilt University (US)
Corresponding author
Shu, Xiao Ou
ORCID
Shu, Xiao Ou
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2009-12-09
Volume
302
Issue
22
Pages
2437
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2009.1783
PMC
PMC2874068
OpenAlex
W2161526842
Cited by
436
References
0
Citations by year
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FWCI
30.08
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01CA118229)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
Keywords
breast cancer survival, soy isoflavones, soy protein, phytoestrogens, breast cancer recurrence, all-cause mortality, estrogen receptor status, cancer survivorship
MeSH terms
Adult, Aged, Breast Neoplasms, Diet, Female, Humans, Middle Aged, Neoplasm Metastasis, Receptors, Estrogen, Glycine max, Tamoxifen, Cohort Studies, Proportional Hazards Models, Antineoplastic Agents, Hormonal, Young Adult

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