Trial Information

Preliminary Study of Endometrial Hyperplasia: Groundwork for a Study to Define an Optimal Classification of Endometrial Carcinoma Precursors

Three systems have been proposed to classify endometrial carcinoma precursors, but it is
currently unclear which system best predicts cancer risk and is most reproducible. The
optimal surrogate endpoint for endometrial carcinoma is therefore unknown. The pathologic
diagnosis of endometrial hyperplasia (EH) includes most suspected immediate precursors and
many mild, highly reversible proliferations. We propose an exploratory study to assess the
feasibility of investigating EH as a source of an endometrial carcinoma surrogate endpoint.

We are conducting a nested case-control study within a large, population-based health care
plan. We will identify cases, defined as women who were diagnosed with EH at least one year
before being diagnosed with endometrial carcinoma or severe atypical hyperplasia at
hysterectomy, through a computerized search of plan databases. We will retrieve the slides
from the matching biopsy and hysterectomy on which carcinoma was diagnosed. Women ages 40
or older who were plan members and received a biopsy or curettage diagnosis of EH between
1970 and 2002 will be eligible to be a case.

We will perform an initial histologic review of cases' index biopsy slides to assess two
types of misclassification known to affect the diagnosis of EH: a) false-negative
endometrial carcinoma (i.e., prevalent carcinoma t the time of EH diagnosis) and b)
false-positive EH (i.e., a benign, non-hyperplastic lesion). From cases' physical records
and linked computer records, we will collect data on histopathologic classification of EH
lesions and subsequent carcinomas; descriptive data (e.g., patient weight, parity, and
menopausal status); and a summary of relevant treatments and follow-up procedures (e.g.,
hormone therapy or additional clinical procedures).

We will select controls, defined as women who were diagnosed with EH but then did not
develop endometrial carcinoma or undergo hysterectomy for a follow-up interval that is
equivalent to the follow-up interval of the cases. Controls will be individually matched to
cases on age at EH diagnosis, date of EH diagnosis, and duration of follow-up, and also
counter-matched based on the original EH diagnosis. After selecting 3 controls per case, we
will assemble the same data from controls: histologic review of original slides, descriptive
data from medical records databases, and treatment and follow-up procedure data from linked
databases.

These data will then be used to estimate the cancer risk associated with specific EH
classifications, identify other patient or clinical factors that might modify those risks,
explore predictors of EH, and explore molecular factors that might influence the probability
of developing carcinoma after a diagnosis of EH.