Plasma enterolactone and breast cancer risk in the Nurses’ Health Study II

Abstract

Background 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. Methods 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 (NHSII) 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). Results Compared to women with enterolactone concentrations ≤ 4nmol/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 2nd to the 4th quartiles, respectively; Ptrend=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); Ptrend=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; Pinteraction=0.02). Conclusions 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.

State of the evidence 2017: an update on the connection between breast cancer and the environment

“…A matched case-control study of mainly premenopausal women in the Nurses’ Health Study II cohort found no overall relationship between plasma enterolactone levels and breast cancer risk. However, in those women whose follicular circulating estradiol levels were below the median, higher enterolactone was associate with a significant decrease in breast cancer risk (OR = 0.49; 95% CI = 0.27–0.91) [ 579 ]. A meta-analysis examining the possible relationship between serum enterolactone levels and either all-cause mortality or breast-cancer associated mortality found negative correlations between the circulating lignan levels and both outcome measures (HR = 0.57; 95% CI = 0.42–0.67 for all-cause mortality and HR = 0.54; 95% CI = 0.39–0.75 for breast cancer mortality [ 580 ].…”

Bioconversion of Pinoresinol Diglucoside and Pinoresinol from Substrates in the Phenylpropanoid Pathway by Resting Cells of Phomopsis sp.XP-8

“…Pinoresinol diglucoside, (+)-1-pinoresinol 4, 4′-di-O-β-D-glucopyranoside ((+)-PDG) is a glycoside lignan compound having various pharmacological functions, including antihypertension [ 1 ], [ 2 ] and prevention of osteoporosis [ 3 ]. After dietary consumption, PDG can be converted by the intestinal microflora to enterolignans [ 4 ], which can potentially reduce the risk of breast cancer [ 5 ] and other hormone-dependent cancers [ 6 ].…”

Prediagnosis plasma concentrations of enterolactone and survival after colorectal cancer: the Danish Diet, Cancer and Health cohort

“…An advantage of present study is that the Danish Diet, Cancer and Health cohort may be a suitable population for research in plant lignans and enterolactone due to a large between-subject variation in plant lignan intake and circulating concentration of enterolactone compared to, for example, cohorts in the USA (38) . High quality information on outcomes and clinical information on tumour characteristics and cancer treatment was available in the present study, with the latter being rare in a cohort setting.…”