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JNCI Journal of the National Cancer Institute 2007 99(6):475-486; doi:10.1093/jnci/djk096
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© The Author 2007. Published by Oxford University Press.

ARTICLES

Dietary Lignan Intake and Postmenopausal Breast Cancer Risk by Estrogen and Progesterone Receptor Status

Marina S. Touillaud, Anne C. M. Thiébaut, Agnès Fournier, Maryvonne Niravong, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon

Affiliations of authors: Institut National de la Santé et de la Recherche Médicale, ERI 20, EA 4045, and Institut Gustave-Roussy, Villejuif, France

Correspondence to: Françoise Clavel-Chapelon, PhD, Institut National de la Santé et de la Recherche Médicale, ERI 20, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France (e-mail: clavel{at}igr.fr).

Background: Studies conducted in Asian populations have suggested that high consumption of soy-based foods that are rich in isoflavone phytoestrogens is associated with a reduced risk of breast cancer. However, the potential associations of other dietary phytoestrogens—i.e., the lignans or their bioactive metabolites, the enterolignans—with the risk of breast cancer are unclear.

Methods: We prospectively examined associations between the risk of postmenopausal invasive breast cancer and dietary intakes of four plant lignans (pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol) and estimated exposure to two enterolignans (enterodiol and enterolactone), as measured with a self-administered diet history questionnaire, among 58 049 postmenopausal French women who were not taking soy isoflavone supplements. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards regression models. Analyses were further stratified by the combined estrogen and progesterone receptor (ER/PR) status of the tumors. Statistical tests were two-sided.

Results: During 383 425 person-years of follow-up (median follow-up, 7.7 years), 1469 cases of breast cancer were diagnosed. Compared with women in the lowest intake quartiles, those in the highest quartile of total lignan intake (>1395 µg/day) had a reduced risk of breast cancer (RR = 0.83, 95% CI = 0.71 to 0.95, Ptrend = .02, 376 versus 411 cases per 100 000 person-years), as did those in the highest quartile of lariciresinol intake (RR = 0.82, 95% CI = 0.71 to 0.95, Ptrend = .01). The inverse associations between phytoestrogen intakes and postmenopausal breast cancer risk were limited to ER- and PR-positive disease (e.g., RR for highest versus lowest quartiles of total plant lignan intake = 0.72, 95% CI = 0.58 to 0.88, Ptrend = .01, 174 versus 214 cases per 100 000 person-years, and RR for highest versus lowest quartiles of total enterolignan level = 0.77, 95% CI = 0.62 to 0.95, Ptrend = .01, 164 versus 204 cases per 100 000 person-years).

Conclusions: High dietary intakes of plant lignans and high exposure to enterolignans were associated with reduced risks of ER- and PR-positive postmenopausal breast cancer in a Western population that does not consume a diet rich in soy.



Context and Caveats

Prior knowledge

High consumption of foods rich in some phytoestrogens, compounds produced by plants that act like estrogens in cells, has been associated with a reduced risk of breast cancer in Asian populations. However, the association between dietary intakes of the lignans, a specific type of phytoestrogen, or their bioactive metabolites and the risk of breast cancer is unclear, particularly among women with intake levels typically found in Western diets.

Study design

A large prospective study in a cohort of French women with a wide range of dietary lignan intakes that examined the association between dietary lignans (assessed with the use of a diet history questionnaire) and the risk of postmenopausal invasive breast cancer.

Contribution

Higher dietary lignan intakes were associated with a reduced risk of postmenopausal invasive breast cancers, particularly those positive for the estrogen receptor and progesterone receptor.

Implications

If the association is found to be causal, increasing dietary lignan intake may be a potential preventive approach for reducing the incidence of breast cancer.

Limitations

Exposure misclassification bias may have resulted in an underestimation of the true associations. The authors could not adjust for unknown potential confounders. Endpoint misclassification with respect to estrogen receptor status was likely. The study cohort was based on a selected population, possibly limiting generalizability of the results to the general population.

 
Manuscript received June 21, 2006; revised January 11, 2007; accepted January 29, 2007.


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