Breast Duct Lavage, Breast Duct Endoscopy, and Gene Expression Profiling in Women With Breast Cancer or Healthy Women Who Are and Are Not at High Risk for Breast Cancer

OBJECTIVES:

Primary

- Compare the incidence and nature of cytologic changes in women with ipsilateral breast
cancer and in healthy women who are and are not at increased risk for breast cancer
using breast duct lavage.

- Characterize high-risk contralateral breast ductal epithelium and architecture in these
women using breast duct endoscopy and correlate these findings with the incidence of
cytologic changes.

- Compare the global gene expression pattern in these participants.

Secondary

- Determine the effects of estrogen replacement therapy on cytology and the gene
expression profile of normal ductal epithelial cells in postmenopausal women by
examining normal epithelial cells before and after initiation of estrogen replacement
therapy.

- Determine the gross genomic alterations present in high risk breast epithelial cells by
comparative genomic hybridization in patients with ipsilateral breast cancer.

- Determine the pattern of protein expression for selected proteins in the high-risk
epithelial cells using proteomics tissue lysate arrays in these patients.

OUTLINE: Participants are stratified according to menopausal status (premenopausal vs
postmenopausal).

Participants undergo breast duct lavage (in the contralateral breast for breast cancer
patients and in either normal breast for healthy volunteers and high-risk subjects) and
breast duct endoscopy.

Participants found to have cytologic atypia may undergo MRI and/or galactography to further
localize or excise the abnormality. Participants with a cytologic atypia not suspected for
malignancy undergo a follow-up lavage and endoscopy in 3-6 months.

Gene expression profiles, comparative genomic hybridization, analysis of miRNA, and
proteomic profiles are conducted on lavage cells.

PROJECTED ACCRUAL: A total of 110 participants (70 breast cancer patients and high-risk
subjects [35 per stratum] and 40 healthy volunteers [20 per stratum]) will be accrued for
this study.