The injection of lidocaine directly into the nipple greatly increases the feasibility of duct cannulation and improves subject comfort. Confirmation of duct cannulation and lavage can be documented with ductoscopy and ultrasound imaging. These procedures can be added to ductal lavage to facilitate its use as a research tool.

The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

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B65 Background The majority of breast cancers originate in the ductal epithelium of the breast. Ductal lavage provides a minimally invasive tool for assessing epithelial cells and their microenvironment. Previous studies of pathological atypical hyperplasia on biopsy, and cytological aypia in nipple aspirate fluid (NAF) and random fine needle aspiration (FNA) have suggested that these cells are precancerous because of the subsequent increased risk of cancer. It has therefore been hypothesized that serial ductal lavage could be used to identify atypia and monitor the effects of chemoprevention over time. This report is part of a larger study examining the differences in hormone levels and cytology between ducts and their reproducibility. This report presents a cohort of women unselected for risk who voluntarily underwent ductal lavage of the same ducts on two occasions six months apart. Samples were analyzed for epithelial cells and macrophages. Methods A total of 107 women were recruited in this IRB-approved prospective study to undergo ductal lavage of three fluid or non-fluid-yielding ducts within a breast. Women were unselected for risk: the average Gail score was 1.67 and ten women had a history of contralateral breast cancer. The average age was 51 years. Fifty-four women were premenopausal, 4 were perimenopausal and 49 were postmenopausal. Samples were submitted in a blinded fashion to a central laboratory and were analyzed by duct for both macrophage and epithelial cell number on Papanicolaou-stained slides. If adequate epithelial cells were present (>10), a diagnosis of each duct (benign, mild atypia, or marked aytpia) was made by an experienced cytopathologist. Results Of the 107 women, 317 (99%) ducts were successfully cannulated without regard to nipple aspirate fluid (NAF) production. Thirty ducts in 23 women were diagnosed with mild or marked atypia on either of the two visits. Of these ducts, 16 were diagnosed at the initial visit and 13 at the second visit. Only one duct was diagnosed with mild atypia on both visits, in a woman with a Gail score of 1.4. Cellular atypia in ductal lavage was not reproducible at a six month interval (p=0.45). This absence of reproducibility was seen in women at all risk levels. Macrophage and epithelial cell numbers also showed a lack of reproducibility at the six month interval (p=0.31 and p=0.22, respectively). Conclusion Atypia on cytology in ductal lavage in women unselected for risk was not reproducible at a six month interval, suggesting that a single diagnosis of atypia on lavage should not be used as a marker for the identification of women at risk. Further studies are necessary to indicate whether persistent atypia over an extended interval could represent an elevated risk for breast cancer. In addition, ongoing studies are being performed to identify better cellular markers of premalignancy and subsequent risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B65.