Abstract
To evaluate the feasibility of nipple aspiration and to identify intermediate markers of breast cancer risk, nipple aspirate fluid (NAF) was collected from 177 subjects using a modified breast pump. The first 33 subjects demonstrated that we could obtain NAF quickly, reliably and repeatedly. Specimens from the remaining 144 subjects were collected to evaluate promising cellular biomarkers. NAF was obtained in 167 out of 177 (94%) subjects overall and in 99% of the 144 most recent subjects. Sufficient NAF was obtained to evaluate cytology in 160 out of 167 (96%) cases and specimens were sufficiently cellular to analyse DNA markers in 53% of cases. Among the last 144 subjects, menopausal status did not influence the ability to obtain NAF. NAF cytology correlated with increased breast cancer risk (P = 0.002). Using computerized image analysis of NAF epithelial cells, DNA index (P = 0.0002), percentage of cells in G2M (P = 0.05) and percentage of cells with hypertetraploidy (P = 0.002) increased as cytology became more abnormal. Our data indicate that NAF can be obtained in essentially all eligible subjects; that breast epithelial cells are evaluable in > 95% of NAF samples for cytology and in over half of NAF samples for DNA index (ploidy) and cell cycle analysis; and that abnormal NAF cytology correlates with increased breast cancer risk. This suggests that biomarkers identified in nipple aspirate fluid may prove useful either as an adjunct to currently accepted breast cancer screening methods, or to evaluate response to a chemopreventive agent.
Highlights
Because of a previous report indicating that nipple aspirate fluid (NAF) was more successful in premenopausal subjects, we evaluated the influence of menopausal status on our ability to obtain NAF
As well as women under 30 or greater than 65 years, were excluded because the success in obtaining NAF from the intact breast in these groups is known to be low (Petrakis, 1993). These subjects were categorized by their risk for breast cancer as having no risk factors, a firstdegree relative with breast cancer, a history of curative treatment for ductal carcinoma in situ (DCIS) or invasive breast cancer, precancerous mastopathy [atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) or recently diagnosed DCIS] or recently diagnosed invasive cancer of the breast
The correlation of breast cancer risk and NAF cytology with a variety of clinical factors, including current use of birth control pills (BCP), current use of hormone replacement therapy (HRT), whether the subject was ever pregnant, the number of livebirths, the number of miscarriages, the subject's difficulty becoming pregnant, the phase of the menstrual cycle in which the sample was obtained and the ease with which NAF was obtained were evaluated. None of these factors correlated with breast cancer risk or NAF cytology, the power of the analysis of current use of birth control pills (BCP) and current use of hormone replacement therapy (HRT) was diminished by having an unbalanced population
Summary
Our goal was to determine the usefulness of NAF cytology in subjects of all risk categories
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