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Endometrial thickness and risk of breast and endometrial carcinomas in the prostate, lung, colorectal and ovarian cancer screening trial.

ABSTRACT: Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas was tested. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55-74 years, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at 1 year (n = 1,018), 2 years (n = 869) and 3 years (n = 641) after baseline. The associations between endometrial thickness and breast (n = 91) and endometrial (n = 14) carcinoma were evaluated by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3-13.8 years). Compared to baseline endometrial thickness of 1.0-2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR = 2.00, 95% CI = 1.15-3.48) and endometrial (RR = 5.02, 95% CI = 0.96-26.36) carcinomas in models adjusted for menopausal hormone use and BMI. These data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas.

SUBMITTER: Felix AS

PROVIDER: S-EPMC3858514 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Endometrial thickness and risk of breast and endometrial carcinomas in the prostate, lung, colorectal and ovarian cancer screening trial.

Felix Ashley S AS Weissfeld Joel L JL Pfeiffer Ruth M RM Modugno Francesmary F Black Amanda A Hill Lyndon M LM Martin Jerry J Sit Anita S AS Sherman Mark E ME Brinton Louise A LA

International journal of cancer 20130828 4

Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas was tested. Endometrial thickness was measured in 1 ...[more]

PMID: 23907658

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Project description:BackgroundThe 5-year overall survival rate of lung cancer patients is approximately 15%. Most patients are diagnosed with advanced-stage disease and have shorter survival rates than patients with early-stage disease. Although screening for lung cancer has the potential to increase early diagnosis, it has not been shown to reduce lung cancer mortality rates. In 1993, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was initiated specifically to determine whether screening would reduce mortality rates from PLCO cancers.MethodsA total of 77 464 participants, aged 55-74 years, were randomly assigned to the intervention arm of the PLCO Cancer Screening Trial between November 8, 1993, and July 2, 2001. Participants received a baseline chest radiograph (CXR), followed by three annual single-view CXRs at the 10 US screening centers. Cancers were classified as screen detected and nonscreen detected (interval or never screened) and according to tumor histology. The positivity rates of screen-detected cancers and positive predictive values (PPVs) were calculated. Because 51.6% of the participants were current or former smokers, logistic regression analysis was performed to control for smoking status. All statistical tests were two-sided.ResultsCompliance with screening decreased from 86.6% at baseline to 78.9% at the last screening. Overall positivity rates were 8.9% at baseline and 6.6%-7.1% at subsequent screenings; positivity rates increased modestly with smoking risk categories (P(trend) < .001). The PPVs for all participants were 2.0% at baseline and 1.1%, 1.5%, and 2.4% at years 1, 2, and 3, respectively; PPVs in current smokers were 5.9% at baseline and 3.3%, 4.2%, and 5.6% at years 1, 2, and 3, respectively. A total of 564 lung cancers were diagnosed, of which 306 (54%) were screen-detected cancers and 87% were non-small cell lung cancers. Among non-small cell lung cancers, 59.6% of screen-detected cancers and 33.3% of interval cancers were early (I-II) stage.ConclusionsThe PLCO Cancer Screening Trial demonstrated the ability to recruit, retain, and screen a large population over multiple years at multiple centers. A higher proportion of screen-detected lung cancers were early stage, but a conclusion on the effectiveness of CXR screening must await final PLCO results, which are anticipated at the end of 2015.

Project description:The impact of lung cancer screening on smoking behavior is unclear. The aims of this ancillary study of the Prostate Lung Colorectal and Ovarian Cancer Screening Trial were to produce risk prediction models to identify individuals at risk of relapse or continued smoking and to evaluate whether cancer-screening variables affect long-term smoking outcomes.Participants completed a baseline questionnaire at trial enrollment and a supplemental questionnaire 4-14 years after enrollment, which assessed several cancer-related variables, including family history of cancer, comorbidities, and tobacco use. Multivariable logistic regression models were used to predict smoking status at completion of the supplemental questionnaire. The models' predictive performances were evaluated by assessing discrimination via the receiver operator characteristic area under the curve (ROC AUC) and calibration. Models were internally validated using bootstrap methods.Of the 31&emsp14;694 former smokers on the baseline questionnaire, 1042 (3.3%) had relapsed (ie, reported being a current smoker on the supplemental questionnaire). Of the 6807 current smokers on the baseline questionnaire, 4439 (65.2%) reported continued smoking on the supplemental questionnaire. Relapse was associated with multiple demographic, medical, and tobacco-related characteristics. This model had a bootstrap median ROC AUC of 0.862 (95% confidence interval [CI] = 0.858 to 0.866) and a calibration slope of 1.004 (95% CI = 0.978 to 1.029), indicating excellent discrimination and calibration. Predictors of continued smoking also included multiple demographic, medical, and tobacco-related characteristics. This model had an ROC AUC of 0.611 (95% CI = 0.605 to 0.614) and a slope of 1.006 (95% CI = 0.962 to 1.041), indicating modest discrimination. Neither the trial arm nor the lung-screening result was statistically significantly associated with smoking outcomes.These models, if validated externally, may have public health utility in identifying individuals at risk for adverse smoking outcomes, who may benefit from relapse prevention and smoking cessation interventions.

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Dataset Information

Endometrial thickness and risk of breast and endometrial carcinomas in the prostate, lung, colorectal and ovarian cancer screening trial.

Publications

Endometrial thickness and risk of breast and endometrial carcinomas in the prostate, lung, colorectal and ovarian cancer screening trial.

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