Dietary lignan intake and postmenopausal breast cancer risk by estrogen and progesterone receptor status.

Journal of the National Cancer Institute

Mar 2007

DOI: 10.1093/JNCI/DJK096

Citations:175

Influential Citations:6

Observational Studies (Human)

Enhanced Details

Methods

Prospective cohort (E3N) of 58,049 postmenopausal French women, aged 41–72 at baseline; observational design; dietary lignan and enterolignan intakes estimated from a validated self-administered diet history questionnaire; outcome: incident primary invasive breast cancer; analyses used multivariable Cox proportional hazards models with stratification by estrogen receptor (ER) and progesterone receptor (PR) status.

Results

Higher total plant lignans and enterolignans were associated with lower risk of postmenopausal breast cancer, particularly for ER+/PR+ tumors. For ER+/PR+ cancers, the highest vs lowest quartile of total plant lignans yielded RR 0.72 (95% CI 0.58–0.88); total enterolignans RR 0.77 (95% CI 0.62–0.95). Lariciresinol showed a significant inverse association with ER+/PR+ cancer (RR 0.82; 95% CI 0.71–0.95). No clear associations with ER−/PR+, ER+/PR−, or ER−/PR− cancers. Conclusion: In Western populations with low soy intake, higher dietary lignan intake may modestly reduce risk of postmenopausal ER+/PR+ breast cancer, supporting a potential preventive role of plant lignans when soy consumption is low.

Limitations

Potential exposure misclassification from self-reported diet; residual confounding; incomplete receptor-status data (~20% without ER/PR status); cohort is selected and highly educated, limiting generalizability; enterolignan exposure estimated indirectly and may not capture individual gut microbiota variation.

Abstract

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 microg/day) had a reduced risk of breast cancer (RR = 0.83, 95% CI = 0.71 to 0.95, P(trend) = .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, P(trend) = .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, P(trend) = .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, P(trend) = .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. show less