Lignans are plant-based
phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast
carcinogenesis. Retrospective studies have observed decreased
breast cancer risk associated with high circulating
enterolactone concentrations, a
biomarker of
lignan intake, but results from prospective studies are conflicting. To prospectively examine this association, we measured plasma
enterolactone levels in 802
breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses' Health Study II cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known
breast cancer risk factors, to calculate relative risks (RR) and 95 % confidence intervals (CI). Compared to women with
enterolactone concentrations ≤4 nmol/L, the multivariate-adjusted RRs for
breast cancer were 1.18 (95 % CI 0.86-1.62), 0.91 (95 % CI 0.66-1.25), and 0.96 (95 % CI 0.70-1.33) for women with
enterolactone levels in the second to the fourth quartiles, respectively; P trend = 0.60. Results were similar across
tumors defined by
estrogen and
progesterone receptor status. Among premenopausal women with follicular
estradiol levels below the median (<47 pg/mL), women in the highest category of
enterolactone levels had a 51 % lower
breast cancer risk compared to those in the lowest category (95 % CI 0.27-0.91); P trend = 0.02. No association was observed among women with high-follicular
estradiol levels (≥47 pg/mL), (comparable RR = 1.39, 95 % CI 0.73-2.65; P interaction = 0.02). We did not observe an overall association between plasma
enterolactone and
breast cancer risk in a large nested case-control study of US women. However, a significant inverse association was observed among premenopausal women with low-follicular
estradiol levels, suggesting that
enterolactone may be important in a low-
estrogen environment. This should be confirmed in future studies.