Preliminary Study of Endometrial Hyperplasia Groundwork for a Study to Define Precursors of Endometrial Cancer
Condition: Endometrial Hyperplasia; Endometrial Cancer; Postmenopausal Bleeding; Vaginal Bleeding
MeSH terms: Endometrial Neoplasms; Endometrial Hyperplasia; Uterine Hemorrhage; Hemorrhage; Hyperplasia
Study type: Observational

Summary: 
      This study, conducted jointly by the National Cancer Institute and the Kaiser Permanente
      Center for Health Research Northwest (KPCHRN) in Portland, Oregon, will lay the groundwork
      for a future study to identify precursors of endometrial cancer; that is, conditions that
      precede development of cancer of the lining of the uterus. The diagnosis of endometrial
      hyperplasia (a condition of abnormal proliferation of endometrial tissue) includes most
      precursors of endometrial cancer, as well as many benign conditions. Currently, three methods
      of classifying endometrial cancer precursors have been suggested based on endometrial
      hyperplasia findings, but it is not known which classification best predicts cancer risk.

      This study will examine surgical specimens of hyperplasia and cancer from women diagnosed
      with endometrial cancer at least 2 years after a diagnosis of endometrial hyperplasia.
      Investigators will estimate the percentage of cases with different degrees of hyperplasia,
      and assess the subsequent cancers that developed. This will allow them to rank hyperplasia
      lesions according to cancer risk and identify lesions that represent the most immediate
      cancer precursors. They will also review patients medical charts for information related to
      cancer risk and treatment.

      Study participants will include women enrolled in the KPCHRN who are 40 years of age or older
      and who were diagnosed with endometrial cancer at least 2 years after being diagnosed with
      endometrial hyperplasia.
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        We are conducting a nested case-control study of adenocarcinoma of the endometrium within a
        retrospective cohort of one large managed health care organization in the Northwest U.S.
        Cases, i.e., women who developed endometrial cancer after a diagnosis of endometrial
        hyperplasia, will be compared with women who were diagnosed with endometrial hyperplasia
        but did not develop cancer during an equivalent follow-up period, after controlling for
        relevant confounders.@@@@@@
      
Biospecimen description: 
      Tissue
    
Keywords: Precursors; Endometrial Cancer; Hyperplasia; Progression