Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Ductal Lavage in Assessing Women With Early Breast Cancer or at High Risk of Developing Breast Cancer and Who Are Eligible For Tamoxifen Therapy

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Diagnostic, Prevention, Treatment Completed 18 to 64 NCI NU-0649-003 NCT00083044

Special Category: SPORE trial

Objectives

1. Evaluate cell morphology and protein expression of breast epithelial cells in ductal lavage samples as a marker of tamoxifen effect from women with breast cancer or from women at high risk for developing breast cancer.
2. Evaluate methylation status of genes previously identified to be related to neoplastic progression of cells in ductal lavage samples from these participants.
3. Evaluate the protein profile of nipple aspiration fluid from these participants before and after treatment with tamoxifen.

Entry Criteria

Disease Characteristics:

• Meets 1 of the following criteria:
  • Diagnosis of small invasive breast cancer
  • Diagnosis of ductal or lobular carcinoma in situ of the breast
  • At high risk for breast cancer (5-year Gail model risk of > 1.6%)



• Eligible for tamoxifen therapy



• No plans for adjuvant chemotherapy



• Prior unilateral early breast cancer allowed*

   [Note: *Only the unaffected breast will be examined during this study]




• Hormone-receptor status:
  • Estrogen receptor-positive (in patients with small invasive breast cancer)

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• More than 6 months since prior chemotherapy

Endocrine therapy

• Concurrent hormone-replacement therapy allowed
• Prior tamoxifen or raloxifene allowed provided treatment duration was no more than 6 months
• At least 1 year since prior raloxifene

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age

• 18 to 64

Sex

• Female

Menopausal Status

• Premenopausal or postmenopausal

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No prior venous thromboembolism

Other

• At least 12 months post-partum
• Not pregnant
• Not nursing within the past 12 months
• No known allergy to lidocaine, prilocaine, or bupivacaine
• No uterine hyperplasia or polyps
• No other contraindication to tamoxifen

Expected Enrollment

A total of 200 participants will be accrued for this study.

Outcomes

Cell morphology and protein expression of breast epithelial cells in duct lavage samples as a marker of tamoxifen effect
Methylation status of genes previously identified to be related to neoplastic progression of cells in ductal lavage samples
Protein profile of nipple aspiration fluid before and after study treatment

Outline

This is a multicenter study.

Participants who are eligible for tamoxifen chemoprevention therapy undergo ductal lavage. Participants are informed of cytological findings and choose to receive oral tamoxifen once daily for 5 years vs observation only. All participants undergo repeat ductal lavage at 6 months. Participants with atypical cytology undergo a third ductal lavage at 12 months.

Mammographic density is measured at study entry and at 12 months.

Ductal cells are analyzed for methylation status of candidate genes.

Participants are followed as clinically indicated.

Bhandare DJ, Nayar R, Masood S, et al.: Reproducibility of ductal lavage findings in high-risk women. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-4015, 2005.

Fackler MJ, Malone K, Schilling E, et al.: Methylated genes in ductal lavage fluid from women with known breast cancer undergoing mastectomy. [Abstract] Breast Cancer Res Treat 94 (Suppl 1): A-2007, S85, 2005.

Bhandare D, Bryk M, Nayar R, et al.: Effect of Tamoxifen (TAM) on estrogen-related biomarkers in ductal lavage (DL) samples a study on follow-up lavages. [Abstract] Breast Cancer Research and Treatment 88 (Suppl 1): A-4031, 2004.

Bhandare D, Golewale N, Geiger A, et al.: Estrogen related biomarkers and cellular atypia in ductal lavage (DL) samples from women at high risk for breast cancer. [Abstract] Breast Cancer Res Treat 82 (Suppl 1): A-1032, S178, 2003.

Didwania A, Golewale NH, Khan SA, et al.: Influence of ductal lavage (DL) findings on tamoxifen decision for high risk women. [Abstract] Breast Cancer Res Treat 82 (Suppl 1): A-1037, S179, 2003.

Bhandare DJ, Khan SA, Motchoulskaia NA, et al.: Isolation of highly purified DNA from low-abundance archived and stained cytological specimens. Clin Chim Acta 367 (1-2): 211-3, 2006.[PUBMED Abstract]

Gorla SR, Steel J, Cohn R, et al.: Impact of surgical resection of primary breast tumor in stage IV breast cancer on local control and survival. [Abstract] J Clin Oncol 23 (Suppl 16): A-629, 35s, 2005.

Li J, Zhao J, Yu X, et al.: Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid. Clin Cancer Res 11 (23): 8312-20, 2005.[PUBMED Abstract]

Golewale NH, Bryk M, Nayar R, et al.: Technical modifications of ductal lavage to improve cell yield. [Abstract] Breast Cancer Research and Treatment 82 (Suppl 1): A-1024, 2003.

Trial Contact Information

Trial Lead Organizations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Seema Khan, MD, Principal investigator		Ph: 312-695-0288 Email: skhan@nmff.org

Registry Information
Official Title		Surrogate Endpoints in Prevention Studies and Ductal Lavage
Trial Start Date		2003-10-01
Registered in ClinicalTrials.gov		NCT00083044
Date Submitted to PDQ		2003-10-24
Information Last Verified		2006-09-17
NCI Grant/Contract Number		CA60553, CA89018

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