Breast Ductal Carcinoma in Situ (DCIS): Reproductive and Hormonal Risk Factors and Reliability of Histologic Diagnoses

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  • March 20, 2019
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  • Phillips, Lynette S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Ductal carcinoma in situ (DCIS) accounts for nearly one-fifth of all newly diagnosed breast cancers in the United States. It comprises a heterogeneous collection of histopathologic characteristics, but reproducibility among pathologists is unknown due to lack of a uniform classification system. Recent data suggests that medium or low-grade (non-comedo type) DCIS differs from high-grade (comedo type) with regard to biological mechanisms, pathology, and risk factors and therefore may not require the same treatment intensity given to more aggressive forms of the disease. Aims of this dissertation were to investigate: 1) agreement by pathologists on histopathologic diagnoses for DCIS subtypes, 2) which of the major diagnostic components contribute most often to each subtype diagnosis, and 3) whether known reproductive and hormonal risk factors for invasive breast cancer are risk factors for DCIS, and if associations differ between comedo and non-comedo DCIS. The dissertation utilized data from the Carolina Breast Cancer Study (CBCS), a populationbased case-control study of in situ and invasive breast cancer. When clinical pathologists rated DCIS histopathologic specimens, agreement was moderate for overall diagnosis and fair for the two most common cellular components characteristic of the disease, pattern of necrosis and maximum nuclear diameter. The most advanced categories for each component were associated with comedo type DCIS, while no uniformity existed for non-comedo type. Case-control analyses examined reproductive and hormonal risk factors for invasive breast cancer and both DCIS subtypes. In general, those decreasing estrogen exposure, such as parity, lactation, older age at menarche and younger age at menopause were inversely associated with disease, whereas factors causing increased estrogen exposure such as oral contraceptive use and postmenopausal hormone replacement therapy use showed increased associations with one or more breast cancer types. Results for comedo type DCIS were similar to invasive breast cancer and differed from noncomedo type for some risk factors. Although the lack of strong diagnostic reliability for DCIS subtypes suggests a potential for error in the risk factor analyses, these results support the division of DCIS cases by subtype for clinical and research purposes and reinforce the need for a universal DCIS classification system.
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  • In Copyright
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  • Millikan, Robert C.
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  • Open access
Date uploaded
  • October 19, 2010

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file details Breast ductal carcinoma in situ (DCIS) : reproductive and hormonal risk factors and reliability of histologic diagnoses 2019-04-12 Public Download