To learn whether a new imaging technology, Contrast-Enhanced Mammography (CEM), compared to standard mammography, can better detect breast cancers in women with dense breasts

Primary Objectives:

• To establish a cohort of 1,000 female MDACC patients with dense breasts who undergo screening contrast-enhanced mammography.
• To establish a comprehensive integrated database of imaging, clinical data, health measurements, and questionnaire data including data from the companion protocol PA17-0584.

Secondary Objectives:

• To perform within-subject comparison of the cancer detection rate between CEM and FFDM.
• To perform within-subject comparison of the sensitivity, specificity, and recall rates of CEM compared to low-energy (LE) images (FFDM equivalent) and compared to a combination of LE and DBT images among women with dense breasts.
• To evaluate the effect of the availability of prior imaging for comparison on the recall rates of CEM, FFDM and DBT.
• In patients who undergo screening breast ultrasound as a standard of care, to evaluate the performance of screening ultrasound for breast cancer detection and compare it with other imaging modalities of CEM, LE images, and DBT.

Exploratory Objectives:

• To combine imaging, blood biomarkers, health measurements and questionnaire data for assessment of breast cancer risk.
• To evaluate if the intensity of background parenchymal enhancement on CEM predicts breast cancer risk in women with dense breasts.
• To evaluate if patients consider CEM as a potentially acceptable imaging modality for routine breast cancer screening.

Inclusion Criteria:

1. Female patients 30-75 years of age with dense breasts (ACR BI-RADS categories C and D) who undergo routine yearly mammography at participating MDACC sites
2. Willingness to co-enroll or currently enrolled in PA17-0584
3. Willingness to participate in the study and ability to provide informed consent

Exclusion Criteria:

1. Self-reported new breast symptoms since last mammogram including nipple discharge, palpable mass, skin dimpling, or focal pain.
2. Current or recent (within the prior 6 months) history of pregnancy or breast feeding
3. Personal history of breast cancer (DCIS or invasive breast cancer)
4. Treatment of any other type of cancer within the past 5 years excluding in-situ cervical and non-melanoma skin cancer
5. Breast biopsy within 6 months
6. Breast surgery within 12 months
7. Breast MRI, MBI, or CEM performed within 24 months
8. Known allergy to iodine-containing contrast agents
9. History of anaphylactic reaction to any substance that required hospitalization or IV placement in a patient with no known prior uneventful exposure to iodine-based IV contrast
10. Renal insufficiency (as defined by UTMDACC policy 3.30- attachment 1 (appendix D)