The reliability of nipple aspirate and ductal lavage in women at increased risk for breast cancer--a potential tool for breast cancer risk assessment and biomarker evaluation.

PURPOSE: Ductal lavage, a technique used to sample epithelial cells from breast ducts, has potential use in risk assessment and biomarker evaluation among women at increased risk for breast cancer. However, little is known about the reliability of the procedure. METHODS: We evaluated the reliability of nipple aspirate (NAF) and ductal lavage at two time points 6 months apart in women at increased risk for breast cancer. Eligible women had a 5-year Gail risk >or=1.66% or lifetime risk of >20%, and/or a family history or personal history of breast cancer. All ducts that produced NAF were cannulated. The kappa statistic was used to evaluate reliability of NAF production, cellular yield, and cytologic diagnosis. RESULTS: Sixty-nine women (mean age, 47 years) were enrolled over 35 months. Forty-seven returned for a second visit. At baseline, 65% of premenopausal and 41% of postmenopausal women produced NAF (P = 0.05), of which 72% underwent successful lavage of at least one duct. Samples of inadequate cellular material for diagnosis were significantly more likely in postmenopausal women than in premenopausal women (P = 0.04). Of the women who returned for a second visit, 18 of 24 who produced NAF had at least one duct successfully cannulated. Twenty-four ducts in 14 women were lavaged twice. Among these ducts, cellular yield for the two time points was inconsistent (kappa = 0.33 +/- 0.13), and only fair cytologic agreement was observed (kappa = 0.32 +/- 0.15). Ductal lavage was associated with moderate discomfort. CONCLUSION: Currently, the use of ductal lavage is limited by technical challenges in duct cannulation, inconsistent NAF production, a high rate of inadequate cellular material for diagnosis, fair cytologic reproducibility, and low participant return rates.

Should women at increased risk for breast and ovarian cancer be randomized to prophylactic surgery? An ethical and empirical assessment.

More information is needed about the relative effectiveness of prophylactic surgery, chemoprevention, and surveillance in reducing breast and ovarian cancer risk in women with an inherited susceptibility mutation. We assessed practical and ethical barriers to conducting randomized clinical trials (RCTs) to compare preventive interventions for breast and ovarian cancer. Eighty-seven at-risk women who attended an education and counseling session about BRCA1/2 testing were asked about their willingness to participate in hypothetical research studies for breast and ovarian cancer risk reduction. In addition, 247 Maryland physicians from five specialties completed a mail survey including a question about their likelihood of recommending RCT participation to an at-risk woman. Nineteen percent of at-risk women reported willingness to participate in a hypothetical RCT for breast cancer risk reduction and 17% for ovarian cancer risk reduction. Women with children and women likely to have a prophylactic mastectomy if found to have a susceptibility mutation were significantly more willing to participate in an RCT. A majority of women would be willing to participate in nonrandomized trials or registries. Fifty-two percent of physicians responded that they would be likely to recommend RCT participation to a woman carrying a breast cancer susceptibility mutation. Oncologists were the most likely to recommend an RCT. Although the results of nonrandomized trials may be difficult to interpret because of such issues as selection bias. Greater feasibility combined with fewer ethical concerns make nonrandomized trials a more viable alternative to randomized trials for evaluation of preventive interventions for breast and ovarian cancer when prophylactic surgery is one of the treatments being evaluated.