Abstract

Abstract Background: Higher endogenous circulating estrogen levels have been linked to elevated risk of breast and endometrial cancers among postmenopausal women, and may also increase risk of ovarian and colorectal cancers. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Previous studies have found that risk factors such as body mass index (BMI) and menopausal hormone use, that appear to operate through estrogenic mechanisms, are directly related to endometrial thickness. Therefore, we tested the hypothesis that endometrial thickness is associated with risk of several sex hormone-related cancers. Methods: Postmenopausal female participants, aged 55-74 years, enrolled at the Pittsburgh site of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial who were screened by transvaginal ultrasound and had known baseline endometrial thickness measurements were included for study (N=1,272). Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We modeled endometrial thickness as a baseline measure, a time-varying covariate, and as a change in endometrial thickness since the most recent ultrasound. Cox proportional hazards regression, with age as the time metric, was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association between endometrial thickness and cancer risk, adjusted for potential confounders. Results: This subcohort (N=1,272) included 91 breast, 14 endometrial, 10 ovarian and 17 colorectal cancers diagnosed after baseline. Median follow-up time was 12.5 years (range: 0.7-13.8 years). At the baseline screen, median endometrial thickness measures were 4.0 millimeters (mm) for breast, 4.5 mm for endometrial, 3.0 mm for ovarian and 4.0 mm for colorectal cancer cases compared to 3.0 mm among women who did not develop cancer. Baseline endometrial thickness, modeled continuously, was associated with risk of breast cancer (RR: 1.08, 95% CI 1.02, 1.14) and endometrial cancer (RR: 1.13, 95% CI 1.02, 1.25) in models adjusted for baseline BMI, hypertension, diabetes, uterine fibroids, marital status, and menopausal hormone use. Similar associations were noted when modeling endometrial thickness as a time-varying covariate [breast cancer (RR: 1.07, 95% CI 1.00, 1.15), endometrial cancer (RR: 1.13, 95% CI 1.00, 1.28)]. No significant association between endometrial thickness and risk of ovarian or colorectal cancer was observed. The change in endometrial thickness since the most recent ultrasound was not associated with cancer risk. Discussion: Our data suggest that transvaginal ultrasound assessments of endometrial thickness, even among asymptomatic women, may be useful in risk prediction of breast and endometrial cancer. Citation Format: Ashley S. Felix, Joel L. Weissfeld, Ruth M. Pfeiffer, Amanda Black, Mark E. Sherman, Louise A. Brinton. Endometrial thickness and risk of sex hormone-related cancers in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 152. doi:10.1158/1538-7445.AM2013-152

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