Clinical trial NCT00083044: Ductal Lavage in Assessing Women With Early Breast Cancer or at High Risk of Developing Breast Cancer and Who Are Eligible For Tamoxifen Therapy
Official title: Surrogate Endpoints in Prevention Studies and Ductal Lavage
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Breast Cancer
Keywords: breast cancer
breast cancer in situ
stage I breast cancer
lobular breast carcinoma in situ
ductal breast carcinoma in situ
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-17
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with early breast cancer or at high risk of developing breast cancer and who are eligible for tamoxifen therapy

Brief summary: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of or treat early cancer. Diagnostic procedures, such as ductal lavage, may improve the ability to assess the effectiveness of chemopreventive drugs, such as tamoxifen, on breast cells and may help doctors plan more effective treatment.

PURPOSE: This phase II trial is studying how well ductal lavage works in assessing changes in breast cells in women with early breast cancer or in those at high risk of developing breast cancer who are eligible for tamoxifen therapy.

Detailed description: OBJECTIVES:

* 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.
* Evaluate methylation status of genes previously identified to be related to neoplastic progression of cells in ductal lavage samples from these participants.
* Evaluate the protein profile of nipple aspiration fluid from these participants before and after treatment with tamoxifen.

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.

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

Eligibility 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)

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

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

Primary outcomes:
measure: Cell morphology and protein expression of breast epithelial cells in duct lavage samples as a marker of tamoxifen effect
timeFrame: Before and after tamoxifen treatment
measure: Methylation status of genes previously identified to be related to neoplastic progression of cells in ductal lavage samples
timeFrame: At time of each ductal lavage.
measure: Protein profile of nipple aspiration fluid before and after tamoxifen treatment
timeFrame: Before and after tamoxifen treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Seema A. Khan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bhandare DJ, Khan SA, Motchoulskaia NA, Melnikov AA, Levenson Chernokhvostov VV. Isolation of highly purified DNA from low-abundance archived and stained cytological specimens. Clin Chim Acta. 2006 May;367(1-2):211-3. doi: 10.1016/j.cca.2005.12.022. Epub 2006 Feb 2. No abstract available.
citation: 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.
citation: Li J, Zhao J, Yu X, Lange J, Kuerer H, Krishnamurthy S, Schilling E, Khan SA, Sukumar S, Chan DW. Identification of biomarkers for breast cancer in nipple aspiration and ductal lavage fluid. Clin Cancer Res. 2005 Dec 1;11(23):8312-20. doi: 10.1158/1078-0432.CCR-05-1538.
citation: 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.
citation: Patil DB, Lankes HA, Nayar R, Masood S, Bryk M, Hou N, Rademaker A, Khan SA. Reproducibility of ductal lavage cytology and cellularity over a six month interval in high risk women. Breast Cancer Res Treat. 2008 Nov;112(2):327-33. doi: 10.1007/s10549-007-9861-8. Epub 2007 Dec 21.
citation: 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.
citation: 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.
citation: 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.
citation: 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.