The association of endogenous pineal hormone melatonin and mammographic breast density in postmenopausal women

Abstract

Background. Mammographic breast density (MBD) is a widely recognized surrogate marker of breast cancer risk and serves as the main dependent variable in our study. Epidemiologic evidence indicates that risk factors shared by breast cancer and mammographic breast density are also factors related to endogenous pineal melatonin which serves as the main independent variable. Experimental studies have consistently demonstrated anticarcinogenic, antiproliferative, antioxidant, and immunostimulating properties of endogenous melatonin. In epidemiologic studies that have investigated the role of melatonin deficiency in the etiology of breast cancer results are not consistent. It has also been reported that women who take aspirin have a lower risk of developing breast cancer but study results vary markedly. Aspirin use serves as our main independent variable in our secondary study of aspirin use and mammographic breast density. Objectives. We examined whether mammographic breast density would be inversely related to nocturnal endogenous melatonin and in a secondary analysis whether inversely related to aspirin use. Design. We recruited 293 postmenopausal women with appointments for screening mammograms at a large western New York state radiological clinic from March 2005 through August 2005 to conduct our cross-sectional study. Screening mammograms were taken during clinic visits and mammographic breast density was measured from digitized images utilizing a validated computer-assisted method. The main metabolite of endogenous melatonin, 6-sulfatoxymelatonin, was measured by radioimmunoassay from overnight urine samples and creatinine-adjusted. Aspirin use and covariate data were collected from interviews, questionnaires, and anthropometric measures taken during clinic visits. Results. The mean age was 58 (SD 6.0), 30% had BMI (kg/m 2 ) classified as obese, and 15% of the women were nulliparous. In a general linear model we observed a marginally significant trend (p 0.04) for categorical melatonin inversely related to percentage mammographic density adjusted for age, BMI, number of full-term pregnancies, and past use of combination hormone replacement therapy. Stratified analysis of aspirin use and non-use yielded a 10% reduction in percentage mammographic density among nulliparous women in the aspirin group (adjusted mean percent density 32.7, 95% CI: 29.9-3.61) compared to non-aspirin users (mean 43.4, 95% CI: 36.7-50.2). Conclusions. The results of this study suggest that nocturnal melatonin secretion may be associated with traditional breast cancer risk factors such as mammographic density, age, BMI, and parity. Aspirin use appeared to be related to lower breast density in postmenopausal women who are nulliparous. The potential to reduce breast cancer risk through lifestyle habits such as the use of aspirin or to minimize the influence of modern disruption of endogenous melatonin warrants further study.