Breast Imaging Studies in Women at High Genetic Risk of Breast Cancer: Annual Follow-Up Study
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Study type: Observational

Summary: 
      This study will explore new screening methods for early detection of breast and ovarian
      cancer in women at high risk for these diseases, because they have an altered breast cancer 1
      (BRCA1) or breast cancer 2 (BRCA2) gene. It will also try to determine if breast tissue
      characteristics in women with a BRCA1 or BRCA2 mutation differ from those in women with a
      normal gene.

      Premenopausal women between 25 and 45 years of age who have participated in National Cancer
      Institute studies for families or individuals at high genetic risk of cancer (78-C-0039 or
      99-C-0081) and who have at least a 50 percent probability of carrying an altered BRCA1 or
      BRCA2 gene may be eligible for this study.

      At the first visit, participants will have from 4 to 24 tablespoons of blood drawn and will
      be interviewed about breast and ovarian cancer risk factors, family and personal history of
      cancer, history of pregnancies, use of oral contraceptives and other hormones and drugs, and
      previous surgery on the breasts and ovaries. In addition, they will undergo the following
      procedures:

      Routine breast and ovarian cancer screening for high-risk women, including a mammogram,
      breast and pelvic exam, instruction in breast self-examination, CA 125 blood test and
      transvaginal ultrasound of the ovaries.

      Magnetic Resonance Imaging (MRI) of the breast MRI uses a strong magnetic field to show
      structural and chemical changes in tissues.

      Breast Duct Lavage In this procedure samples of fluid and cells from the lining of the breast
      milk ducts are collected to look for cancerous or pre-cancerous cell changes.

      Positron Emission Tomography (PET) scan PET scanning will be done only in participants whose
      mammogram or MRI findings require additional evaluation. This diagnostic test is based on
      differences in how cells take up and use glucose (sugar), one of the body s main fuels.

      Annual follow-up visits will be scheduled for 3 years and will include routine high-risk
      screening as described above, blood draw, update of family history and risk factors, breast
      MRI, breast duct lavage and, if there are changes on the MRI or mammogram that need further
      evaluation, the PET will be repeated.

      ...
    

Detailed description: 
      Background:

        -  Women who carry mutations in genes such as BRCA1/2 have a higher lifetime risk of breast
           cancer (BC) and are at risk of developing BC at earlier ages than women in the general
           population.

        -  Prophylactic mastectomy and/or oophorectomy may be used to decrease risk and intensified
           mammographic and magnetic resonance imaging (MRI) surveillance may allow earlier
           diagnosis; however, prophylactic mastectomy has not been shown to convey survival
           advantage over more conservative management.

        -  Greater breast tissue density and low BC incidence result in a lower positive predictive
           value of mammography in premenopausal women as compared to postmenopausal women
           (PPV=0.04 for women aged 40-49).

        -  This study explores whether high-risk breast imaging phenotypes may be identified by
           comparing imaging characteristics of mutation carriers/non-carriers using two imaging
           modalities: mammography and MRI.

        -  Nipple Aspiration Fluid collection (NAF) and breast duct lavage will be used to obtain
           cytologic materials which may be used as an adjunct to breast imaging for the early
           detection of epithelial atypia and pre-invasive cancer.

      Objectives:

        -  Compare four outcomes including two mammographic density measures (qualitative and
           semiquantitative), fibroglandular volume measure using MRI, and contrast enhancement
           measure using MRI (both semiquantitative) in mutation carriers/non-carriers to improve
           lesion detection

        -  Explore non-ionizing approaches (MRI) to BC screening because the effects of ionizing
           radiation due to mammography are unknown.

        -  Use NAF and/or BDL to obtain epithelial cell samples and correlate cytologic and imaging
           findings.

        -  Gather prospective data on the transformation from
           normal/hyperplastic/pre-invasive/invasive disease in BRCA1/2 mutation
           carriers/non-carriers through molecular/genetic studies of breast tissue (via biopsy of
           radiographic abnormalities) or breast fluid (via BDL and/or nipple aspiration) and
           develop molecular markers for early detection of epithelial atypia/pre-invasive cancer.

        -  Assess the psychosocial impact of participation in a BC screening program.

      Eligibility:

        -  Women 25-56 years of age carrying a known BRCA1/2 deleterious mutation.

        -  Women between the ages of 25 -56 who are first- or second- degree relatives of
           individuals with a deleterious BRCA1/2 mutation.

        -  Women aged 25-56 who are first- or second- degree relatives of individuals with
           BRCA-associated cancers in families with documented BRCA mutations.

      Design:

        -  Prospective cohort study of 200 women to gather data on the evolution of epithelial
           cell/molecular changes in BRCA1/2 mutation carriers, by collecting/analyzing NAF, BDL
           fluid, biopsy tissues (when indicated), and serum/lymphocytes; samples are stored for
           future studies.

        -  Women complete questionnaires and undergo breast/pelvis examination, transvaginal
           ultrasonography, serum pregnancy test, fasting glucose, electrolytes, BUN, creatinine
           and CA 125. Standard four view mammogram and breast MRI are performed on study entry and
           annually for three additional years.
    

Intervention name(s): 2-Fluorodeoxyglucose
Intervention type(s): Drug
Intervention MeSH terms: Fluorodeoxyglucose F18
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study explores whether high-risk breast imaging phenotypes may be identified by
        comparing imaging characteristics of mutation carriers /non-carriers using two imaging
        modalities: mammography and MRI. This is a prospective cohort study of 200 women to gather
        data on the evolution of epithelial cell/molecular changes in BRCA1/2 mutation carriers, by
        collecting/analyzing NAF, BDL fluid, biopsy tissues (when indicated), and
        serum/lymphocytes; samples are stored for future studies. Eligible study participants
        include: 1)Women 25-56 years of age carrying a known deleterious mutation; 2)
        BRCA1/2@@@Women between the ages of 25 56 who are first- or second- degree relatives of
        individuals with a deleterious mutation. BRCA1/2, and 3)Women aged 25-56 who are first- or
        second- degree relatives of individuals with associated cancers in families with documented
        BRCA- BRCA mutations.
      
Keywords: Breast MRI; Nipple Aspirate Fluid; Transvaginal ultrasound; Ductal lavage