Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Comparison of Genes in Healthy Women, Women at High Risk for Breast Cancer, and Women With Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
No phase specified	Genetics	Closed	18 and over	NCI	NCI-00-C-0079 NCT00023608

Objectives

1. Determine the risk of breast cancer associated with polymorphisms in genes involved in estrogen metabolism and action.
2. Determine the relationship between susceptibility genotypes and environmental risk factors for each tumor type.
3. Determine the biomarkers of breast cancer risk and/or early detection in nipple fluid, blood, and tissues.
4. Determine whether breast density and polymorphisms in genes are associated with estrogen metabolism and action.

Entry Criteria

Disease Characteristics:

• Meets the criteria for one of the following groups:
  • Documented history of invasive breast cancer
  • Documented history of ductal carcinoma in situ
  • Normal health (control group), meeting all of the following criteria:
    • No prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix
    • Pedigree Assessment Tool (PAT) score < 8
    • Gail risk < 1.67
  • High risk for breast cancer, meeting the following criteria:
    • No prior malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix AND meeting at least 1 of the following criteria:
      • Estimated risk of developing breast cancer over the next 5 years > 1.66 by the Gail Model
      • Documented deleterious mutation in BRCA1 or BRCA2
      • PAT score ≥ 8
      • History of lobular carcinoma in situ
      • History of atypical lobular or ductal hyperplasia



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age:

• Adult

Sex:

• Female

Menopausal status:

• Pre- or postmenopausal

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Expected Enrollment

A total of 3,000 women (1,000 healthy, 1,000 at high risk for breast cancer, and 1,000 with breast cancer) will be accrued for this study.

Outcomes

Risk of breast cancer associated with polymorphisms in genes involved in estrogen metabolism and action as measured by personal health history, cancer family history , risk factor history, food frequency questionnaire, and blood sample at study entry

Risk biomarkers as measured by nipple aspirate collection at study entry
Correlate breast density and polymorphisms in genes associated with estrogen metabolism and action as measured by mammogram at study entry

Outline

Participants donate a blood sample and complete an epidemiological, dietary, and family history questionnaire. Participants who have undergone biopsy or surgery for breast cancer are asked to authorize the use of their tissues.

Participants who have had a routine film screen mammogram within the past year are asked to submit their most recent mammogram for breast density determination.

Participants warm their breasts with a warm moist washcloth over approximately 30 minutes, then undergo nipple fluid aspiration over 15 seconds, up to 5 times per breast. Women who have any active infection or superficial inflammation of the breast or who are currently lactating or less than 6 months post-lactation do not undergo nipple fluid sampling.

Restriction fragment length polymorphism analysis, simple tandem repeat polymorphism analysis, automated fluorescent genotyping, and single-stranded conformation polymorphism analysis are used to test for genes associated with the biosynthesis and metabolism of estrogen (COMT1, CYP1A1, CYP1A2, CYP2D6, CYP2E1, CYP3A4, CYP17, CYP19, EPHX1, EPHX2, NAT1, NAT2, NQO1, AHR, UDPGT, GSTA1, GSTA2, GSTA3, GSTM1, GSTM2, GSTM3, GSTM5, GSTP1, GSTT1, GSTT2, GSTX1, and GSTX2).

Two-dimensional gel electrophoresis, laser capture microdissection, and surface-enhanced laser desorption ionization spectroscopy are used to test for vitamin D receptor and members of the homocysteine/methionine metabolism family, methylenetetrahydrofolate reductase, methionine synthase, and cystathione beta synthase in nipple fluid, blood, and tissue.

Participants do not receive the results of the genetic testing and these results are not kept in their medical records.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Giuseppe Giaccone, MD, PhD, Principal investigator		Ph: 301-496-4916

Registry Information
Official Title		Susceptibility to Breast Cancer
Trial Start Date		2001-06-15
Trial Completion Date		2008-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00023608
Date Submitted to PDQ		2000-03-23
Information Last Verified		2009-01-07

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