Clinical Trial: Nuclear Morphology of Breast Cells in Ductal Lavage

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

Official Title: Morphometry of Breast Cells in Ductal Lavage

Brief Summary: Breast nipple aspirate fluids (NAF) are useful for non-invasive monitoring of the breast. NAF has been shown to exhibit large inter-individual differences in lipid peroxidation. Unfortunately, the yield of epithelial cells in NAF is low. More recently, breast ductal lavage has been approved for clinical use. Nuclear morphologic features of breast biopsies have been shown previously to have prognostic value for breast cancer risk. In women without cancer, there may be subtle changes in the breast epithelial cells that can only be defined with computer-assisted measurements. The subjects selected for this study will be 98 women with biopsy-confirmed proliferative breast disease. These women are at slightly increased breast cancer risk, and exhibit higher mean levels of cholesterol and cholesterol oxides in NAF than women with non-proliferative histology in the breast. Levels of 8-isoprostane, cholesterol, fatty acids, fat-soluble micronutrients and 2,6-cyclolycopene-4,5-diol will be quantified in breast NAF that is obtained before breast lavage. These measures were chosen based on their potential relationship to dietary intakes and to oxidative stress, which is relevant to the application of these methods to dietary prevention studies.The investigators will characterize the morphology of breast epithelial cells from lavage using quantitative image cytometry to capture nuclear and cellular area, diameter, roundness, perimeter, and nuclear:cytoplasmic area ratio. Correlations will be evaluated between the measured morphologic features and each analyte in the NAF. The impact of various clinical, demographic and dietary factors on cellular morphology will also be explored. This study will help establish the feasibility of using these measures as endpoints in dietary intervention studies and will generate hypotheses that should be tested in larger studies. Such measures also should be applicable to molecular epidemiological investigations that seek to examine the impact of

Detailed Summary:

WHY THE STUDY IS BEING DONE

Breast nipple aspirate fluids (NAF) can be obtained non-invasively from women, making analyses of this fluid relevant to studies of breast cancer risk. The inter-individual variation for lipid oxidation products (a type of damage to fats) in NAF is more than 100-fold, and these oxidation products are likely to have a toxic effect on the breast epithelial cells. During breast ductal lavage, NAF is first aspirated, and the ducts producing fluid are then subjected to lavage to obtain epithelial cells. The nuclear features (morphology) of these cells can then be examined. Nuclear morphology is a quantitative method to observe subtle changes in nuclear features, and these measures in benign breast biopsies have been shown to have prognostic value for breast cancer risk.

This exploratory study will help establish the feasibility of using these measures as endpoints in dietary intervention studies. Since the differences in lipid oxidation levels in NAF are markedly large, it is reasonable to believe that there must be some influence on nuclear morphology. These measures also should be applicable to investigations that seek to examine the impact of certain genetic polymorphisms and environmental exposures on biomarkers of oxidative stress and breast cancer risk.

We will study women who have been diagnosed previously with proliferative breast disease. These women may be good candidates for dietary prevention studies since they are at somewhat increased risk of breast cancer, receive little beyond surgery for treatment, and have been shown to have higher levels of lipid oxidation in the breast than women with no such diagnosis.

WHAT WE HOPE TO ACCOMPLISH

We
Sponsor: University of Michigan

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: University of Michigan

Dates:
Date Received: November 28, 2005
Date Started: June 2004
Date Completion:
Last Updated: December 19, 2012
Last Verified: November 2008