OBJECTIVES:
Primary
* Determine the diagnostic yield of whole breast bilateral screening ultrasound and mammography for the detection of breast cancer in women at high risk for breast cancer.
* Determine the cancer detection yield of a single contrast-enhanced magnetic resonance imaging (MRI) examination after 3 rounds of annual screening with ultrasound and mammography in these participants. (MRI component of the study)
Secondary
* Determine the independent sensitivity and specificity of these screening methods in these participants.
* Correlate performance of these screening methods with selected participant characteristics (e.g., breast density and heterogeneity of the parenchyma).
* Validate the sonographic classification of lesions as "probably benign" and estimate the rate of malignancy in participants screened with these methods.
* Determine the cost effectiveness associated with screening breast ultrasound, in terms of radiologist and resource time performing the exam and the induced cost of screening ultrasound (e.g., follow-up and biopsy).
* Determine the reproducibility of lesion identification, measurement of lesion diameters, and volume and recording of lesion location on ultrasound in these participants.
* Determine the size, type, grade, and nodal status of cancers seen only on MRI in these participants. (MRI component of the study)
* Estimate the rate of benign biopsies and short interval follow-up induced only by MRI in these participants. (MRI component of the study)
* Determine the cost effectiveness of MRI, including induced costs of unnecessary biopsies and follow-up. (MRI component of the study)
* Compare the agreement among multiple examiners in sonographic, mammographic, and MRI feature analysis (using terms from the BI-RADS® lexicon) and final assessment (e.g., estimated probability of malignancy and/or recommendation for biopsy) in the enriched set of diagnostic training cases with consensus and histopathologic reference standards.
OUTLINE: This is a randomized, multicenter study. Participants are randomized to 1 of 2 screening arms.
* Arm I: Participants undergo physician-performed bilateral whole breast ultrasound (US) followed by mammogram within 2 weeks.
* Arm II: Participants undergo mammogram followed by physician-performed bilateral whole breast US within 2 weeks.
In both arms, participants with negative or benign findings are rescreened according to their screening arm at 1 and 2 years. Participants with "probably benign" findings are rescreened at the 6-month follow-up visit. Participants with findings that are suspicious or highly suggestive of malignancy are recommended for biopsy.
A subset of participants\* in both arms undergo contrast-enhanced breast MRI within 4 weeks after completion of the 2-year screening US and mammogram. Participants with "probably benign" findings seen only on MRI may undergo an additional breast MRI at the 6-month follow-up visit. Participants with additional suspicious lesions seen only on MRI undergo second-look targeted US for biopsy guidance or MRI-guided vacuum-assisted biopsy after completion of any biopsies or additional views prompted by the 2-year screening US and mammogram visit.
NOTE: \*No diagnosis of metastatic cancer of any type since entering this clinical trial.
Participants are followed annually for 3 years.
PROJECTED ACCRUAL: A total of 2,808 participants will be accrued for this study within 2 years.
