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


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Sponsored by:	National Cancer Institute (NCI)
Information provided by:	Warren G Magnuson Clinical Center (CC)

Women who carrying a BRCA1 or BRCA2 gene mutation or who are the first- or second-degree relative of an individual with a BRCA-associated cancer in a family documented to have a BRCA1 or BRCA2 mutation will be eligible for enrollment into this pilot study of breast cancer screening modalities. 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, breast MRI and PET scan will be scheduled initially during either the follicular or mid-luteal phase of the menstrual cycle. A unilateral cranio-caudal mammogram, and bilateral MRI and PET scan 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); (3) a semiquantitative measure of contrast enhancement (MRI); and (4) FDG uptake measured over time (PET scan). 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. Consent for a PET study will be requested if an abnormality is detected on mammography or breast MRI requiring additional clinical or radiographic follow-up.

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

Condition	Treatment or Intervention
Breast Cancer Healthy Ovarian Cancer	Drug: 2-Fluorodeoxyglucose

Women who carrying a BRCA1 or BRCA2 gene mutation or who are the first- or second-degree relatives of individuals with a BRCA-associated cancer in a familiy documented to have a BRCA1 or BRCA2 gene mutation will be eligible for enrollment into this pilot study of breast cancer screening modalities. 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, breast MRI and PET scan will be scheduled initially during either the follicular or mid-luteal phase of the menstrual cycle. A unilateral cranio-caudal mammogram, and bilateral MRI and PET scan 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: (1) two measures of mammographic density (qualitative and semiquantitative); (2) a semiquantitative measure of fibroglandular volume (MRI); (3) a semiquantitative measure of contrast enhancement (MRI); and (4) FDG uptake measured over time (PET scan) to determine if these measures vary between the follicular and the mid-luteal phases. On the initial- and three-month visit, all participants will undergo nipple aspiration. Those participants who express nipple aspiration fluid will undergo breast duct lavage. Participants will be seen annually in a manner analogous to the Annual Follow-up Study for an additional three years. A physical exam, standard four-view mammography, breast MRI, CA 125, transvaginal color doppler ultrasonography and breast duct lavage will be done annually. Consent for a PET study will be requested if an abnormality is detected on mammography or breast MRI requiring additional clinical or radiographic follow-up.

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.

INCLUSION CRITERIA
To participate in the Menstrual Cycle Pilot Study, a woman must:
Must be at least 25 years of age (or 5 years younger than the age at diagnosis of the youngest family member with a tumor associated with the Breast-Ovarian Cancer Syndrome) and less than 56 years of age.
Must be premenopausal as determined by menstrual history (no change in menstrual pattern in prior 6 months) and an FSH level less than 15 mIU/ml obtained on the third day of the menstrual cycle.
Must be a known mutation carrier or be a first- or second-degree relative of an individual with a tumor associated with the Breast-Ovarian Cancer Syndrome in a family with a known BRCA mutation.
Have undergone genetic counseling and risk assessment.
Agree to release of genetic test result for stratification purposes, whether or not she has chosen to receive individual test results for clinical decision-making.
Have an ECOG performance status of 0-1.
Have a normal fasting blood glucose (for PET studies only).
Be able to provide informed consent.
EXCLUSION CRITERIA
A history of menstrual cycle irregularities over the previous 6 months, including history of cycles less than 26 days or more than 35 days.
Use of the following drugs within 6 months prior to study entry: steroids, selective estrogen receptor modulators (SERMs) or hormonal agents (including tamoxifen, raloxifene, estrogen, DHEA, anabolic steroids, oral contraceptives, depoprovera, progestin IUD, oral progestins, norplant, or drugs to induce ovulation.
Pregnancy or lactation within 12 months of enrollment.
Abnormal CA-125 level.
History of invasive cancer except for non-melanoma skin cancer or cervical carcinoma in situ.
History of diabetes (excluded from PET studies only).
Creatinine greater than 2.
Previous bilateral mastectomy or bilateral radiation therapy.
History of DCIS or LCIS .
Weight over 136 kilograms.
Allergy to gadolinium.
Allergy to lidocaine or Marcaine (bupivacaine) (excluded from breast duct lavage only).
Medical or psychiatric disorder which, in the opinion of the Principal Investigator, would preclude informed consent or ability to participate in clinical research.