Recent changes in endometrial cancer trends among menopausal-age US women
Introduction
Endometrial cancer is the fourth most common cancer among women and the most common gynecological cancer in the US [1]. Multiple lines of evidence suggest that endometrial cancer is related to excess exposure to estrogens relative to progesterone, especially for the most common type of endometrial cancers (termed Type I) [2]. Specifically, elevated endogenous estrogen levels may mediate the increased endometrial cancer risk associated with postmenopausal obesity [3], and use of estrogen-only menopausal hormone therapy (MHT) is contraindicated among women with intact uteri because of its link to marked increases in endometrial cancer incidence [3]. In contrast, continuous regimen estrogen plus progestin MHT (26 days or more of progestin per month) is associated with a decreased endometrial cancer risk relative to non-hormone use [4].
In 2002, the Women's Health Initiative (WHI) randomized trial was stopped early due to an increased risk of breast cancer and other adverse events [5]. As a result of extensive media coverage there was a subsequent precipitous decline in usage of estrogen plus progestin MHT [5]. Following the decrease in estrogen plus progestin MHT use, breast cancer incidence fell rapidly [6]. Endometrial cancer incidence rates after the decline in MHT use have not been comparably analyzed. Using data from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) we evaluated trends in endometrial cancer incidence before and after the early termination of the WHI trial and the resultant decrease in MHT use.
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Materials and methods
Data on endometrial cancer incidence was obtained from the National Cancer Institute's SEER 13 registries for the years 1992–2009 [7]. SEER 13 data is estimated to cover 13.8% of the US population and includes the following cancer registries: Atlanta, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Utah, San Francisco-Oakland, Seattle-Puget Sound, Los Angeles, San Jose-Monterey, rural Georgia and the Alaska Native Tumor Registry. We identified endometrial cancer cases as primary tumors that
Statistical analysis
Using SEER*Stat 8.0.10 software (National Cancer Institute, Bethesda, MD), incidence rates of endometrial cancer per 100 000 woman-years were age-standardized to the US population in 2000. The annual percent change (APC) was calculated for two time periods: before (1992–2002) and after (2003–2009) the early termination of the WHI trial. Rates were estimated for women ages 20–49 (n = 10 936) and 50–74 (n = 52 492), approximating pre- and postmenopausal groups.
For women 50–74 years old, we evaluated
Results
In contrast to the constant endometrial cancer incidence rate pattern observed from 1992 to 2002 in women ages 50–74 (APC, 0.0%; 95% CI, −.5%, 0.5%), rates increased after 2002 among this age group (APC, 2.5%; 95% CI, 1.4%, 3.6%; PAPC comparison < 0.01) (Fig. 1). A different pattern was observed among women ages 20–49, with rates increasing over the entire time period (1992–2002: APC, 1.1%; 95% CI, 0.3%, 2.0%; 2003–2009: APC, 2.1%; 95% CI, 0.7%, 3.5%; PAPC comparison = 0.21). In lag analyses, the
Discussion
We observed increases in endometrial cancer incidence rates following the early termination of the WHI trial in 2002. This pattern was strongest among women in the age group most likely to use MHT, women 50–74 years old. Recently an evaluation of nationwide incidence rate trends among women of all ages between 1999 and 2006 reported a relatively stable rate of invasive uterine cancers [8]. While not directly comparable, the increasing incidence rate patterns in our study that were not observed
Conflict of interest statement
The authors declare no conflicts of interest.
Acknowledgement
This work was supported by the Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services.
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