Comparison of Breast Cancer Screening With Dual-Energy Contrast-Enhanced Spectral Mammography to Digital Breast Tomosynthesis in Women With Dense Breasts (Contrast Mammography Imaging Screening Trial

Inclusion Criteria: * 1\. Women must have mammographically dense breasts, ACR BI-RADS® lexicon categories c or d (heterogeneous or extreme fibroglandular tissue) on their most recent prior screening. * 2\. Women agree to not undergo whole breast screening ultrasound for the duration of the trial until the year 2 standard of care imaging. * 3\. Women must not have symptoms or signs of benign or malignant breast disease (e.g., bloody, or clear nipple discharge, breast lump, focal breast pain). * 4\. Women must be able to undergo intravenous (IV) administration of iodinated contrast (e.g., no contraindication to intravenous contrast administration for Omnipaque \[iohexol\], and no known allergy-like reaction to iodine or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology \[ACR\]: https://www.acr.org/-/media/ACR/files/clinical-resources/contrast\_media.pdf). * 5\. Women must not be pregnant or breast-feeding. All females of childbearing potential who are uncertain if they could be pregnant or may be pregnant or as per local site standard of practice in women undergoing DBT and CESM must have a negative blood test or urine pregnancy test prior to Omnipaque (iohexol) administration. A female of childbearing potential is any woman, regardless of sexual orientation, sexual identity or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months). * 6\. Women of childbearing potential must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the following year until the Year 1 DBT and CESM studies are performed. Exclusion Criteria: * 1\. Women currently undergoing treatment for breast cancer, or planning surgery for a high-risk lesion (ADH, ALH, LCIS, papilloma, radial scar). * 2\. Women who have had the following are not eligible: 1. a mammogram less than 11 months prior to study entry. 2. screening breast ultrasound within 11 months prior to study entry. 3. breast MRI less than 36 months prior to study entry. 4. contrast-enhanced spectral mammography less than 36 months prior to study entry. 5. molecular breast imaging (MBI) less than 36 months prior to study entry. 6. breast prosthetic implants (silicone or saline). 7. suspected of being at high-risk for breast cancer, as defined by the ACS breast MR screening recommendations (lifetime risk of ≥20%-25%) unless they are unable to undergo an MRI. (Reference Appendix I) 8. a history of sickle cell disease. * 3\. Women with known or suspected renal impairment. Requirements for glomerular filtration rate (GFR) determination prior to IV iodinated contrast administration are determined by local site standard practice. Criteria that should be considered include, but are not limited to, the following: * Age \>60 years old * History of renal disease, including dialysis, kidney transplant, single kidney, renal cancer, and renal surgery * History of hypertension requiring medical therapy * History of diabetes mellitus * Use of metformin or metformin-containing drug combinations * 4\. Women who are pregnant, breast feeding, or planning to become pregnant from screening until 30 days after the last administration of Omnipaque (iohexol). * 5\. Large breasted women that require multiple images per standard view of the breast (Tiling) as determined by their most recent mammogram.