Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer.
BACKGROUND
Ductal lavage is a method of minimal epithelial sampling of the breast, with potential utility for repeat sampling and biomarker analysis in chemoprevention studies. We report here the baseline findings from a study designed to assess the utility of ductal lavage in this setting.


METHODS
Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides. Additional slides were immunostained for estrogen receptor (ER) alpha, Ki-67, and cyclooxygenase-2, and the labeling index (LI) was established by counting negative and positive cells. The ductal lavage supernatant (DLS) was assayed for estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6, and epidermal growth factor (EGF).


RESULTS
One hundred sixty-eight women have entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by woman (averaging data across all ducts). Mild atypia was seen in 43 of 145 (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed significant positive correlations between ECN and cytologic atypia, ER LI, cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly associated with estrogenic precursors, ER LI and ECN. A factor representing the DLS hormone and protein variables explained 36% of the variance; total ECN was highest when factor score and ER LI were high and was lowest when both were low (P for interaction = 0.001).


CONCLUSIONS
Biomarker analyses in epithelial cells and DLS are feasible. The significant associations of EGF with other markers suggest a possible role in increasing epithelial cell mass.
Bhandare
Deepa
D
Lynn Sage Breast Center, 675 North St. Clair, Galter 13-174, Chicago, IL 60611, USA.
Nayar
Ritu
R
Bryk
Michele
M
Hou
Nanjiang
N
Cohn
Rachel
R
Golewale
Nazar
N
Parker
Noah P
NP
Chatterton
Robert T
RT
Rademaker
Alfred
A
Khan
Seema A
SA
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000209:etiology* / Q000517:prevention & control*; D002402:Cathepsin D / Q000032:analysis; D018890:Chemoprevention; D004815:Epidermal Growth Factor / Q000032:analysis*; D004847:Epithelial Cells; D004958:Estradiol / Q000032:analysis; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D008875:Middle Aged; D011374:Progesterone / Q000032:analysis; D012016:Reference Values; D012307:Risk Factors; D007507:Therapeutic Irrigation
D014408:Biomarkers, Tumor; D015850:Interleukin-6; D011374:Progesterone; D004958:Estradiol; D004815:Epidermal Growth Factor; D002402:Cathepsin D