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

Alternate Title

Imaging Procedures in Women With a Genetic Risk For Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs No phase specified Genetics, Screening Closed 25 to 56 NCI NCI-01-C-0009 NCT00012415

Objectives

Primary

1. Determine whether breast imaging outcome measures can be used to define a high-risk imaging phenotype in women who are BRCA1 or BRCA2 mutation carriers or non-carriers.
2. Assess the use of positron emission tomography imaging of breast lesions detected by mammography or magnetic resonance imaging, normal contralateral breast tissue, and normal ovarian tissue in BRCA1/2 carriers or non-carriers.
3. Assess the use of breast duct lavage to obtain epithelial cell samples for cytologic evaluation and molecular/genetic studies in high-risk premenopausal women.
4. Compare imaging findings with histologic or cytologic findings from these participants.

Secondary

1. Determine the psychosocial impact of participation in an intensive breast cancer screening program on these participants.
2. Assess prior breast cancer screening practices in these participants.
3. Determine participant burden (distress, pain, and/or discomfort) in regards to specific procedures used in the course of the study (breast duct lavage, nipple aspiration, mammography, and breast MRI).
4. Determine participants perceptions of uncertainty and its determinants regarding the results of their cancer screening tests.
5. Determine the effect of a positive BRCA mutation test result on participants attitudes and intentions regarding the formation and maintenance of permanent couple relationships.

Entry Criteria

Disease Characteristics:

• Meets one of the following criteria:
  • Known carrier of BRCA1 or BRCA2 mutation
  • First- or second-degree relative of an individual known to carry a deleterious BRCA1 or BRCA2 mutation
  • First- or second-degree relative of an individual with a tumor associated with Breast-Ovarian Cancer Syndrome in a family with known BRCA mutation



• Has undergone genetic counseling and risk assessment



• No abnormal CA 125 level



• No bilateral breast cancer, ovarian cancer (any stage), or stage IIB or greater breast cancer within the past 5 years
  • Ductal carcinoma in situ or stage I-IIA breast cancer allowed provided the following are true:
    • At least 6 months since completion of prior primary therapy (surgery, radiotherapy, and/or chemotherapy)
      • Tamoxifen or aromatase inhibitor adjuvant therapy allowed
    • No local relapse after prior primary treatment unless patient has been relapse free for 5 years before study entry



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics
• No prior bilateral radiotherapy to the breasts

Surgery:

• See Disease Characteristics
• No prior bilateral mastectomy or oophorectomy
• No prior subareolar (e.g., papilloma resection or biopsy or fine needle aspiration within 2 cm of the nipple) or other surgery to the breast being studied which might have disrupted the ductal system (ductal lavage patients only)
• No breast implants

Other:

• No prior silicone injection to the breast being studied

Patient Characteristics:

Age:

• 25 (or 5 years younger than the age at diagnosis of the youngest family member with a tumor associated with Breast-Ovarian Cancer Syndrome) to 56

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1

Life expectancy:

• At least 6 months

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Creatinine ≤ 2 mg/dL

Cardiovascular

• No cardiac complications, including any of the following:
  • Myocardial infarction within the past year
  • Cerebrovascular accident within the past year
  • Unstable or uncontrolled angina
  or

Other:

• Must agree to release results of genetic counseling for stratification purposes
• Normal fasting blood glucose (for positron emission tomography [PET] study only)
• Weight less than 136 kg (299 lbs)
• Clinically stable to complete the full 3-month course of vaccination based on the opinion of the study investigator
• No allergy to gadolinium, lidocaine, or bupivacaine
• No history of diabetes (for PET study only)
• No other invasive cancer within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No medical or psychiatric disorder that would preclude study participation or giving informed consent
• Not pregnant or nursing within the past 6 months
• No active infection or inflammation of the breast being studied

Expected Enrollment

Approximately 200 participants (100 BRCA1/2 mutation carriers and 100 BRCA1/2 mutation non-carriers) will be accrued for this study.

Outcomes

Correlate mammographic density (qualitative and semiquantitative) and semiquantitative fibroglandular vol. of DCE-MRI in mutation carriers and non-carriers by annual mammogram and MRI of the breast

Positron emission tomography (PET) imaging of breast lesions usually detected by mammography or breast MRI prior to breast biopsy
PET imaging of normal ovarian tissue in BRCA1 and BRCA2 mutation carriers and non-carriers prior to breast biopsy
Breast duct lavage as measured by cytology reports annually
Carcinogenesis of breast cancer in mutation carriers and non-carriers as measured by breast biopsy and breast duct lavage annually or as indicated
Histologic and cytologic findings as measured by cytology and pathology reports
Analysis of MRI screening of women at high genetic risk for breast cancer as measured by MRI reports annually
Psychosocial impact of participation in study treatment as measured by the Center for Epidemiologic Studies Depression scale (CESD), BSl-18, Intrusive Thoughts Scale, and Cancer Worry Scale annually
Prior breast cancer screening techniques as measured by a pre-visit self-administered questionnaire and pre-visit telephone interview at baseline
Tolerability and burden of participation in study treatment as measured by an questionnaire, CESD, and BSL-18 during study treatment and annually thereafter
New tools in assessing family communication patterns and mutuality among high risk women as measured by CEGRAM annually
Patient's perceptions of uncertainty regarding the results of cancer screening test and explore the psychological effects and determinants of these uncertainty perceptions as measured by uncertainty questionnaire, Need for Cognition (NFC) questionnaire and Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire during each imaging visit

Outline

Participants undergo a physical exam, including exam of breast and pelvis, standard four-view mammogram, breast magnetic resonance imaging (MRI), CA 125 level determination, and transvaginal color doppler ultrasonography. Participants with abnormal mammogram and/or MRI results are asked to undergo positron emission tomography scans of the breast and asymptomatic ovaries. Breast duct lavage fluid is collected from all participants for cytologic analysis. Participants undergo repeat screening studies annually for 3 years.

Participants are followed annually.

Abati A, Greene MH, Filie A, et al.: Quantification of the cellular components of breast duct lavage samples. Diagn Cytopathol 34 (1): 78-81, 2006.[PUBMED Abstract]

Kriege M, Brekelmans CT, Boetes C, et al.: Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351 (5): 427-37, 2004.[PUBMED Abstract]

Peters JA, Kenen R, Giusti R, et al.: Exploratory study of the feasibility and utility of the colored eco-genetic relationship map (CEGRM) in women at high genetic risk of developing breast cancer. Am J Med Genet A 130 (3): 258-64, 2004.[PUBMED Abstract]

King BL, Tsai SC, Gryga ME, et al.: Detection of chromosomal instability in paired breast surgery and ductal lavage specimens by interphase fluorescence in situ hybridization. Clin Cancer Res 9 (4): 1509-16, 2003.[PUBMED Abstract]

Podo F, Sardanelli F, Canese R, et al.: The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk. J Exp Clin Cancer Res 21 (3 Suppl): 115-24, 2002.[PUBMED Abstract]

Dooley WC, Ljung BM, Veronesi U, et al.: Ductal lavage for detection of cellular atypia in women at high risk for breast cancer. J Natl Cancer Inst 93 (21): 1624-32, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

NCI - Division of Cancer Epidemiology and Genetics

Jennifer Loud, Principal investigator		Ph: 301-594-8062

Related Information

Web site for additional information
Featured trial article

Registry Information
Official Title		Breast Imaging Screening Studies in Women at High Genetic Risk of Breast Cancer: Annual Follow-up Study
Trial Start Date		2002-08-04
Registered in ClinicalTrials.gov		NCT00012415
Date Submitted to PDQ		2000-11-02
Information Last Verified		2008-09-02

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