Dietary Soy Linked to Lower Risk for Breast Cancer Death, Recurrence

Laurie Barclay, MD

December 08, 2009

December 8, 2009 — Dietary soy intake among Chinese women with breast cancer is significantly associated with lower risk for death and recurrence, according to the results of a large, population-based cohort study reported in the December 9 issue of the Journal of the American Medical Association.

"Soy foods are rich in isoflavones, a major group of phytoestrogens that have been hypothesized to reduce the risk of breast cancer," write Xiao Ou Shu, MD, PhD, from Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues. "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."

The study goal was to determine the association of dietary soy intake after diagnosis of breast cancer with total mortality and cancer recurrence. In the Shanghai Breast Cancer Survival Study of 5042 female breast cancer survivors in China, women 20 to 75 years of age who were diagnosed between March 2002 and April 2006 were recruited and followed up through June 2009.

At about 6 months after cancer diagnosis, participants provided information on cancer diagnosis and treatment, lifestyle exposures after cancer diagnosis, and disease progression. Three follow-up interviews at 18, 36, and 60 months after diagnosis allowed updating of this information. To obtain survival information for participants who were lost to follow-up, the investigators used annual record linkage with the Shanghai Vital Statistics Registry database. Disease and treatment information were verified from medical record review.

Primary study endpoints were total mortality and breast cancer recurrence or breast cancer–related deaths. Adjustment for known clinical predictors and other lifestyle factors was performed using Cox regression analysis, with dietary soy intake treated as a time-dependent variable. Median follow-up was 3.9 years (range, 0.5 - 6.2 years).

During follow-up of 5033 breast cancer patients treated with surgery, there were 444 deaths and 534 recurrences or breast cancer–related deaths. Soy food intake, measured by either soy protein or soy isoflavone intake, was inversely associated with mortality and recurrence. Compared with the lowest quartile of intake of soy protein intake, the hazard ratio for the highest quartile 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. For women in the lowest and highest quartiles of soy protein 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. Women with either estrogen receptor–positive or estrogen receptor–negative breast cancer exhibited this inverse association, as did both users and nonusers of tamoxifen.

"Among women with breast cancer, soy food consumption was significantly associated with decreased risk of death and recurrence," the study authors write.

Limitations of this study include a relatively short follow-up period and limited statistical power for subanalyses, such as estrogen receptor status or tamoxifen use status.

"In this population-based prospective study, we found that soy food intake is safe and was associated with lower mortality and recurrence among breast cancer patients," the study authors conclude. "The association of soy food intake with mortality and recurrence appears to follow a linear dose-response pattern until soy food intake reached 11 grams/day of soy protein; no additional benefits on mortality and recurrence were observed with higher intakes of soy food. This study suggests that moderate soy food intake is safe and potentially beneficial for women with breast cancer."

In an accompanying editorial, Rachel Ballard-Barbash, MD, MPH, from the National Cancer Institute in Bethesda, Maryland, and Marian L. Neuhouser, PhD, from the Fred Hutchinson Cancer Research Center in Seattle, Washington, note differences between China and the United States in the quality, type, and quantity of soy food intake. Differences in screening rates and other factors in China compared with the United States may also preclude comparisons of stage- and treatment-specific results.

"Even though the findings by Shu et al suggest that consumption of soy foods among breast cancer patients is probably safe, studies in larger cohorts are required to understand the effects of these foods among diverse clinical subgroups of breast cancer patients and survivors," the editorialists write. "In the meantime, clinicians can advise their patients with breast cancer that soy foods are safe to eat and that these foods may offer some protective benefit for long-term health. Moreover, the potential benefits are confined to soy foods, and inferences should not be made about the risks or benefits of soy-containing dietary supplements."

The US Department of Defense Breast Cancer Research Program and the National Cancer Institute supported this study. Dr. Shu reports having received a research development fund from the United Soybean Board in 2005. The other study authors and editorialists have disclosed no relevant financial relationships.

JAMA. 2009;302:2437-2443, 2483-2484.

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