Evaluation and management of the woman with an abnormal ductal lavage.

RATIONALE FOR DUCTAL LAVAGE The majority of breast cancers originate in the epithelial lining of the ductal system of the breast. Studies of ductal carcinoma in situ (DCIS), a lesion accepted as the precursor of invasive carcinoma, strongly suggest that the early changes of malignancy occur in a segmental fashion within a ductal system rather than diffusely throughout the breast. Multiple peripheral papillomas, a lesion associated with an increased risk of breast cancer development, also occur in a segmental distribution. This anatomic distribution, coupled with the prolonged time period from detection of low-grade DCIS to development of invasive carcinoma, suggests that examination of the ductal cells might be an effective method for identifying women at increased risk for developing breast carcinoma. Ductal lavage is a minimally invasive diagnostic tool that has been developed to identify evidence of cellular atypia in breast ducts. In the initial multicenter trial, 507 women at increased risk for breast cancer development on the basis of a personal history of breast cancer, or a 5-year Gail model risk of breast cancer development of 1.7% or more were studied. Fluid-yielding ducts were identified by nipple aspiration, and a microcatheter was inserted into each fluid-yielding duct and infused with 2 to 6 mL of normal saline. The effluent was collected, and the lavage procedure repeated until approximately 10 mL of saline were instilled into each duct. Cytologic diagnoses from nipple aspiration and ductal lavage were compared as the primary endpoint of the study. The procedures were well tolerated, and there were no serious adverse events. Fluid-yielding ducts were identified in 85% of subjects. Only 27% of specimens obtained by nipple aspiration contained an adequate number of epithelial cells for diagnosis, with a median of 120 epithelial cells per breast. In contrast, 78% of specimens from ductal lavage had adequate cells for diagnosis, with a median of 4,000 or 13,500 epithelial cells per duct, depending on the type of catheter used for lavage. Both these differences were highly statistically significant (p 0.001). A total of 24% of subjects had abnormal lavages, with 17% showing mild atypia, 6% moderate atypia, and in two cases ( 1%), frankly malignant cells. This study clearly demonstrates that ductal lavage is a safe and effective technique for collecting epithelial cells from the breast ductal system. This is an important finding for translational researchers because it provides an opportunity to test these cells for molecular markers that can predict development of the fully malignant phenotype, and to sample the same duct repeatedly over time. But this study has also raised many questions for clinicians and women at risk for developing breast cancer. In particular, these include the reproducibility of cytologic interpretations of lavage fluid, how to integrate the findings of ductal lavage into current clinical methods of risk assessment, the role of ductal lavage as a diagnostic tool for breast cancer, and the workup needed for the finding of atypia on ductal lavage. This article will review these subjects.