Breast Imaging Screening Studies in Women at High Genetic Risk of Breast Cancer: Annual Follow-up Study
- 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
- 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.
- 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
- 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
- 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.
- 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.
- 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
- 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.
Jennifer T Loud, C.R.N.P.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|