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Ductal Lavage Is an Inefficient Method of Biomarker Measurement in High-Risk Women

Authors' Affiliations: Departments of ¹ Surgery, ² Preventive Medicine, and ³ Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; and ⁴ Department of Pathology, University of Florida College of Medicine, Jacksonville, Florida

Requests for reprints: Seema A. Khan, Department of Surgery, Northwestern University, 303 East Superior Street, Lurie 4-133, Chicago, IL 60611. Phone: 312-503-2112; Fax: 312-503-2555; E-mail: skhan{at}nmh.org.

Effective methods of serial epithelial sampling to measure breast-specific biomarkers will aid the rapid evaluation of new preventive interventions. We report here a proof-of-principle phase 2 study to assess the utility of ductal lavage (DL) to measure biomarkers of tamoxifen action. We enrolled women with a 5-year breast cancer risk estimate >1.6% or the unaffected breast of women with T_1a or T_1b breast cancer. After entry DL, participants chose tamoxifen or observation and underwent repeat DL 6 months later. Samples were processed for cytology and immunohistochemistry for estrogen receptor , Ki-67, and cyclooxygenase-2. Of 182 women recruited, 115 (63%) underwent entry and repeat DL; 85 (47%) had sufficient cells for analysis from 1 duct at both time points; in 78 (43%), cells were sufficient from 1 matched ducts. Forty-six women chose observation and 39 chose tamoxifen. We observed greater reductions in the tamoxifen group than in the observation group for Ki-67 (adjusted P = 0.03) and estrogen receptor (adjusted P = 0.07), but not in cyclooxygenase-2 (adjusted P = 0.4) labeling. Cytologic findings showed a trend toward improvement in the tamoxifen group compared with the observation group. Interobserver variability for cytologic diagnosis between two observers showed good agreement ( = 0.44). Using DL, we observed the expected changes in tamoxifen-related biomarkers; however, poor reproducibility of biomarkers in the observation group, the 53% attrition rate of subjects from recruitment to biomarker analyses, and the expense of DL are significant barriers to the use of this procedure for biomarker assessment over time.

Key Words: biomarkers • breast cancer risk • ductal lavage