Breast Imaging Studies in Women at High Genetic Risk of Breast Cancer: Menstrual Cycle Study

Asymptomatic, premenopausal women are (1) known carriers of an altered BRCA1 or BRCA2 gene, or (2) first- or second-degree relatives of individuals with a BRCA-associated cancer in a family documented to have a BRCA1 or BRCA2 gene mutation will be eligible for inclusion in this pilot study to assess new approaches to early detection of breast and ovarian cancer in high-risk women. We will recruit up to fifty women (twenty-five women who carry an altered BRCA1 or BRCA2 gene and 25 non-carriers matched by age and family mutation type) with regular menstrual cycling (documented by menstrual history and premenopausal FSH level). A physical exam including exam of the breast and pelvis, a standard four view mammogram and breast MRI will be scheduled initially during either the follicular or mid-luteal phase of the menstrual cycle. A unilateral cranio-caudal mammogram and bilateral MRI will be repeated three months after entry during the phase not initially studied. A CA125 and transvaginal color doppler ultrasonography will be done in the follicular phase. Carriers and non-carriers will be compared with respect to menstrual cycle differences in: (1) two measures of mammographic density (qualitative and semiquantitative); (2) a semiquantitative measure of fibroglandular volume (MRI); and (3) a semiquantitative measure of contrast enhancement (MRI). On the initial and three-month visit, all participants will undergo breast duct lavage to investigate if there are consistent menstrual cycle differences in breast ductal cytologies. Participants will be seen annually thereafter for an additional three years of follow-up. A physical exam, standard four-view mammography, breast MRI, CA 125, transvaginal color doppler ultrasonography and breast duct lavage will be done annually. Participants in the Menstrual Cycle Pilot Study, will complete a self-administered questionnaire and telephone interview and will complete periodic follow-up questionnaires to assess various behavioral and psychosocial endpoints. As part of the Menstrual Cycle Pilot Study, we will recruit 25 volunteers to assist in training study investigators in performing breast duct lavage. Cytologies obtained from volunteers will be used to develop oncogene probe panels to be used in the study.