Presence of epithelial cells in nipple aspirate fluid is associated with subsequent breast cancer: A 25-year prospective study

Fluid and epithelial cells obtained from the breasts of non-pregnant, non-lactating women by nipple aspiration, can be used for early diagnosis of breast neoplasms. However, since nipple aspirate fluid (NAF) with cells is obtainable from less than half of women sampled, the question arises: Is this method capable of targeting the women most likely to develop breast cancer? We approached this question with a 25-year prospective study to determine if subjects yielding NAF with or without epithelial cells were more likely to develop breast cancer during the follow-up period than subjects from whom no NAF or epithelial cells were obtained. Logistic regression analysis was used to determine relative risk (RR) with 95% confidence intervals (CI). The follow-up cohort of 972 was representative of the eligible cohort of 1605 for factors related to breast cancer risk and nipple aspiration outcome, and representative of the general population for breast cancer risk. After a mean follow-up period of 25 years, women with epithelial cells in NAF were significantly more likely to develop breast cancer (RR=1.92; CI=1.22-3.01; p <= 0.005), especially invasive breast cancer (RR=2.27; CI=1.27-4.03; p <= 0.005), than women with no NAF, or NAF without epithelial cells. These risks were higher for women < 55 years of age at the time of sampling (RR=2.1 for any breast cancer, 2.5 for invasive breast cancer). We conclude that presence of NAF with epithelial cells is associated with subsequent breast cancer risk and may be a useful marker for women at higher risk.