A Clinical Study to Evaluate Somo•v and Digital Mammography Together as a Breast Cancer Screening Method, Compared to Digital Mammography Alone, in Women With Dense Breasts.

This is a study to determine if having somo٠v™ (U-Systems, Inc.) Automated Breast Ultrasound (ABUS) done together with a routine screening mammogram, is more sensitive to detecting breast cancer in women with dense breast tissue than getting a routine screening mammogram without ABUS. Potential study volunteers will be recruited at participating breast centers from the cohort of asymptomatic women who are scheduled to undergo routine screening mammography.

Breast cancer is one of the most commonly diagnosed cancers in American women with an estimated 210,000 new cases diagnosed in 2007. Death rates in women with breast cancer are much lower when the cancer is detected at an early stage, and less intense forms of treatment can be used at early stages when cancerous lesions are the smallest. It is for this reason that annual routine mammograms are recommended by the American Cancer Society for women 40 years of age and older and are the current standard of care for breast cancer screening.

One thing that is known to interfere with the early detection of breast cancer with mammograms is a woman's breast density. Women under age 50 tend to have more density in their breasts than women who are older, but density may be present in women of all ages and is estimated to exist in 40% to 60% of all women who have mammograms. Women who have more fibrous connective and glandular tissue than fatty tissue in their breasts have more breast density.

Breast density can make breast cancer difficult for a radiologist to see on a mammogram. Also, research has shown that women who have dense breast tissue are more likely to develop breast cancer in their lifetime than women who do not have dense breast tissue. Automated Breast Ultrasound (ABUS) is a breast imaging technology which is less affected by a woman's breast density, and is currently FDA approved for use by doctors and sonographers as an adjunct to mammography. ABUS is most commonly used in the diagnostic setting, when a woman has a known breast abnormality or symptom.

This study will try to determine if ABUS can be a clinically beneficial element of routine breast screening in women who do not have any known abnormalities or symptoms, but do have dense breast tissue which could impact the accuracy of their yearly mammograms. Unlike mammography, ABUS does not use radiation. ABUS uses sound waves at a safe frequency to create pictures of the internal breast tissue. Ultrasound has been shown to find cancer not visible with mammography in women with dense breasts. The ABUS used in this study automatically scans the breast and may help detect cancers in dense tissue.

All women who volunteer to participate in this study and who also meet the study requirements will receive ABUS in addition to their routine screening mammogram. The outcome of this screening will be recorded and followed for up to one year. Study participation will be finished at the completion of the next annual routine mammogram, or the diagnosis of breast cancer, whichever comes first.

More than 50,000 women will be invited nationwide to provide informed consent and be screened for eligibility to participate. More than 20,000 women will meet the primary inclusion requirement of having > 50% dense breast tissue and will be enrolled in this study.

Volunteers who decide to participate in this study must agree to the following:

• To have all routine standard care that is recommended by the study doctor, which may include diagnostic procedures like additional imaging or a biopsy, OR, if the results of screening (ABUS and XRM) are negative (normal or benign), agree to complete an annual routine screening mammogram one year from now and notify the study doctor if any breast changes or symptoms develop during this year.
• To be contacted by the study doctor, or one of the study staff members, if the recommended follow-up procedures are incomplete or if the volunteer does not return to the clinic in one year for an annual routine screening mammogram.
• To have an Automated Breast Ultrasound (ABUS), if the screening mammogram indicates dense breast tissue. ABUS will require the patient to lay comfortably on her back for approximately 10 minutes while the ultrasound is being performed. The study includes as many as three ultrasound scans of each breast, each scan lasting one minute. Unlike a mammogram, ABUS does not involve any mammography-like compression. Instead, the breast will be lightly pressed against the patient's body during the scan. If the mammogram shows that the breast tissue is not dense, the volunteer will not be eligible for further participation in the study and will not undergo an ABUS. The participant will still receive the same standard care and treatment she would normally receive.
• To complete a Study Participant Questionnaire and allow the study doctor to collect the following information from the medical records: breast health history, cancer treatment history, mammogram results, ABUS results, results of biopsy or aspiration, diagnosis and the outcome of follow-up mammogram one year later. Information, like name, date of birth and medical record number will be removed by the study doctor and/or clinic staff before these data are reported and analyzed.

Participating in this study will take approximately 30 minutes in addition to the time a participant would normally spend in the office. This time will be spent learning about the study, providing informed consent and receiving ABUS. In order for the study doctors to gather data on the accuracy of mammography and ABUS, they will need to collect the mammography and ABUS results, as well as results from any other breast evaluations, procedures or testing performed for the next year, until the completion of an annual routine mammogram, the results of which will also be recorded.

There are no known, harmful effects of breast ultrasound, although the procedure itself may be uncomfortable for women with breasts which are tender or sensitive to gentle pressure. If an abnormality is seen on the ABUS examination or on the mammogram, the study doctor may recommend additional tests, which are the standard of care and might include a biopsy. If any potential abnormalities are observed from the ABUS that are not seen on the standard mammogram, the participant and the study doctor will be informed and any testing that may be ordered as a result of the abnormal ABUS will be the same standard tests that would be ordered for an abnormal mammogram.Other risks of participating in the study include:

• Unknown risks. There may be risks or side effects which are unknown at this time and participation in the study may involve additional risks that are currently unknown.
• Loss of confidentiality. Just as with other medical information from routine medical care, all study related information will be kept as confidential as possible. Study information will be kept in locked files and in databases with password protected access. Participant names and any other identifying information will not be released from the clinic and it will not be used in any published reports about this study. There is a need to share protected health information with the study staff at the clinic and because of this, absolute confidentiality cannot be guaranteed.

Women who are pregnant or nursing a child may not take part in this study. Women who become pregnant during the duration of the study will be withdrawn.

There is no guarantee that participants will receive any direct benefit from being in this study. There is a possibility that ABUS may be better in detecting early breast cancer than mammogram or physical examination alone. Early detection of breast cancer may lead to more effective treatments in the future.

This study presents subjects with the opportunity to receive ABUS at no additional cost to them or their insurance when they would otherwise not be entitled to this benefit. Currently, ABUS is FDA approved as an adjunct to mammography and is most commonly used in women who have known breast abnormalities; those women are not eligible for the study. Women who choose not to participate in the study, and women who are not eligible for the study, will not receive a screening ABUS exam at no cost to them or their insurance.

All study participants will be helping us evaluate a specific use for the FDA approved ABUS system: screening women with dense breasts. If ABUS is proven to improve early breast cancer detection rates in women with dense breast tissue, the standard of care for breast screening may change so that all women with dense breast tissue may receive ABUS as part of standard care in addition to screening mammography, and will reduce the number of women who die from breast cancer every year. If no improvement in breast cancer is proven, the standard of care will not change and future patients and doctors will benefit from the knowledge that routine screening mammography is the most effective program for early breast cancer detection.

Participants will not be reimbursed for their time in participating in this study and they will not receive any payment for participating in the study.

The sponsor, U-Systems, Inc., will pay for this research study and provide funding to the study doctor for study related procedures and management of the study records.

Inclusion criteria

• Female
• Asymptomatic
• Prior screening mammograms, if available, exhibit history of breast density
• Not currently pregnant or breastfeeding
• Not planning to become pregnant in the following 18 months
• Age 25 or older
• No breast surgeries or interventional procedures in the past 12 months
• No history of cancer diagnosis and/or treatment in the past 12 months
• Informed Consent and Completed Participant Questionnaire
• Complete screening mammography views (CC and MLO) for one or both breasts
• > 50% preliminary parenchymal density on preliminary assessment by technologist
• Willing to comply with study protocol and follow-up recommendations:

• If evaluation is normal, must undergo routine screening mammography in 12 months
• If evaluation is abnormal, must undergo additional imaging and diagnostic procedures recommended by the Investigator, including but not limited to a biopsy and routine screening mammogram in 12 months if findings are benign.
• Agrees to report any breast changes or symptoms to the Investigator for the 12 months following study enrollment until and including completion of routine screening mammogram.
• Agrees to be contacted by site study staff if routine screening mammography or recommended follow-up is not completed within the recommended time frame.

Exclusion criteria

• ≤ 50% preliminary parenchymal density on preliminary assessment by technologist
• Does not meet all Inclusion Criteria for Enrollment