title: Ductal lavage is an inefficient method of biomarker measurement in high-risk women.
abstract: 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 T1a or T1b 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 alpha, Ki-67, and cyclooxygenase-2. Of 182 women recruited, 115 (63%) underwent entry and repeat DL; 85 (47%) had sufficient cells for analysis from > or =1 duct at both time points; in 78 (43%), cells were sufficient from > or =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 alpha (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 (kappa = 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.
authors.affiliation: Department of Surgery, Feinberg School of Medicine, Northwestern University, 303 East Superior Street, Lurie 4-133, Chicago, Illinois 60611, USA. skhan@nmh.org
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.forename: Deepa B
authors.initials: DB
authors.lastname: Patil
authors.forename: Michele
authors.initials: M
authors.lastname: Bryk
authors.forename: Nanjiang
authors.initials: N
authors.lastname: Hou
authors.forename: David
authors.initials: D
authors.lastname: Ivancic
authors.forename: Ritu
authors.initials: R
authors.lastname: Nayar
authors.forename: Shahla
authors.initials: S
authors.lastname: Masood
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis* / Q000097:blood*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis*; D003584:Cytological Techniques; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D015588:Observer Variation; D012306:Risk; D013629:Tamoxifen / Q000627:therapeutic use; D007507:Therapeutic Irrigation; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D013629:Tamoxifen