Breast Imaging Studies in Women at High Genetic Risk of Breast Cancer: Annual Follow-Up Study

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.