Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

• Published in: International journal of cancer Vol. 130; no. 6; pp. 1401 - 1410
• Main Authors: Zaineddin, Aida Karina, Vrieling, Alina, Buck, Katharina, Becker, Susen, Linseisen, Jakob, Flesch-Janys, Dieter, Kaaks, Rudolf, Chang-Claude, Jenny
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.03.2012; Wiley-Blackwell; Wiley Subscription Services, Inc
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - blood; Biological and medical sciences; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - metabolism; Cancer; Case-Control Studies; Cohort Studies; Confidence intervals; enterolactone; Epidemiology; ErbB-2 protein; Estrogen receptors; Estrogens; Estrogens - metabolism; Gynecology. Andrology. Obstetrics; Health risk assessment; Humans; lignans; Lignans - blood; Lignans - metabolism; Logistic Models; Mammary gland diseases; Medical research; Medical sciences; Meta-analysis; Middle Aged; Monoclonal antibodies; Population studies; Post-menopause; postmenopausal women; Postmenopause - blood; Progesterone; Progesterone - metabolism; Prospective Studies; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Risk Factors; Studies; Targeted cancer therapy; Tumors; Women; Xenoestrogens; Antineoplastic agent; Human; Estrogen receptor; Breast disease; postmenopausal women; Enterolactone; Breast cancer; Malignant tumor; Monoclonal antibody; Progesterone receptor; lignans; Phytoestrogen; Mammary gland diseases; Cancerology; Risk factor; Postmenopause; Adult; Female; Lignan; Serum; Woman; Trastuzumab; Cancer; Hormonal receptor
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.26157

Lignans are a group of estrogenic compounds present in plants. Several epidemiological studies proposed that lignans may protect against breast cancer by exerting anticarcinogenic activity. Levels of enterolactone were determined in serum samples of 1,250 cases and 2,164 controls from a large population‐based case–control study. We assessed the association between serum enterolactone and postmenopausal breast cancer risk using conditional logistic regression accounting for potential risk and confounding factors. Fractional polynomials were used to determine the function that best fitted the data. Moreover, we assessed heterogeneity by estrogen/progesterone/herceptin (ER/PR/HER2) status of the tumor. Additionally, a meta‐analysis with seven further studies addressing enterolactone concentrations and breast cancer risk was performed. Postmenopausal breast cancer risk decreased with increasing serum enterolactone levels [highest compared to lowest quintile: [odds ratio = 0.65; 95% confidence interval (CI) 0.52–0.83, ptrend = <0.0001]. A significant inverse association for ER+/PR+ as well as ER−/PR− tumors was observed, with a significantly stronger association for ER−/PR− tumors (pheterogeneity = 0.03). The association for ER−/PR− tumors did not differ by expression of HER2 (pheterogeneity = 0.3). The meta‐analysis yielded a significant reduced pooled risk estimate of: 0.66; 95% CI: 0.55–0.77) comparing the highest to the lowest quantiles of enterolactone levels. We found strong evidence for a significant inverse association between serum enterolactone and postmenopausal breast cancer risk, which was stronger for ER−PR− than for ER+PR+ tumors but not differential by further expression of HER2. The overall evidence together with other studies supports an inverse association between higher serum enterolactone levels and postmenopausal breast cancer risk.