Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Healthy women presenting to enrollment sites for routine annual mammographic examinations, confirmed to have BI-RADS category c or d breast composition (density).

Routine screening mammography exam, CC + MLO views.

Routine Full-Field Digital Mammography

Routine screening tomosynthesis exam, CC + MLO views.

Routine Digital Breast Tomosynthesis

Bilateral breast ultrasound performed as an adjunct to mammography.

Automated Whole Breast Ultrasound

Mary W Yamashita, MD

The SoftVue™ is a whole breast ultrasound system with an automated scanning curvilinear ring-array transducer that employs UST. It is currently cleared under FDA 510(k) K123209 and K142517 for use as both a B-mode ultrasonic breast imaging system and color imaging of transmission data (sound speed and attenuation). SoftVue™ is not intended to be used as a replacement for screening mammography.

SoftVue uses non-ionizing ultrasound energy to generate tomographic image volumes of the whole breast. While the patient lays prone on a padded table with one breast comfortably submerged in a bath of warm water, a ring-shaped transducer, 22 cm in diameter, encircles the breast and pulses low-frequency sound waves through the water and into the breast tissue. More than 2000 elements in the curvilinear transducer's 360 degree array emit and receive ultrasound signals to analyze echoes from the breast anatomy in all directions, from the chest wall to the nipple. Not only does SoftVue capture data from the reflection of the sound waves off of tissue boundaries and structures within the breast, but because the transducer surrounds the whole breast, SoftVue also captures signals that are transmitted through the breast. This additional transmission data enhances the visualization of the anatomic structure of the breast tissue and is not currently available in any other commercially marketed breast ultrasound device.

This prospective, multicenter, multi-arm, clinical case collection program is IRB-approved and will be conducted in compliance with Good Clinical Practice, the Declaration of Helsinki and all applicable regulatory requirements. Arm 1 aims to collectively enroll up to 17,500 women at a total of up to 8 clinical sites. The design of this protocol is strictly limited to case collection; all investigational and statistical plans for future analyses will be prepared and registered separately, if they are applicable to the requirements of FDAAA 801.

Arm 1 is limited to the cohort of asymptomatic women, with heterogeneously or extremely dense breast parenchyma (BI-RADS breast composition category c or d). Matched triads of 2D digital mammography (FFDM), 3D digital mammography (DBT), and SoftVue automated whole breast ultrasound (SV)exams, from the same patient, with demographic information and clinical outcome data, will be collected during the same screening imaging episode. Ultrasound characteristics for all types of lesions, whether they are benign or malignant, will be collected, as well as objective and subjective breast density composition data.

The exams and clinical data accumulated in this prospective case collection (PCC) protocol will populate a database from which future investigations may be designed for peer reviewed publication, development of user training curriculums, building teaching case, and creating new marketing materials for SoftVue.A subset of exams will be sampled from Arm 1 for use in ROC Reader Study (protocol DMT-2015.002), which will be separately registered and is designed to evaluate the safety and efficacy of a new screening indication for use of SoftVue™ as an adjunct to screening mammography. The results of this ROC Reader Study will be submitted to the FDA for their consideration of a PMA application for SoftVue.

MEDICAL DEVICES:

* SoftVue™ (SV) automated whole breast ultrasound system, 510(k) Cleared for B-Mode ultrasound breast imaging, manufactured by Delphinus Medical Technologies.
* SoftVue™ with device modifications (software, hardware, user-interface), safety-tested for human use to complete feasibility, verification, and validation testing as a routine part of product development and performed in accordance with FDA 21 CFR 812.2 (b), manufactured by Delphinus Medical Technologies.
* Full-field digital mammography (FFDM), FDA Approved for breast screening and diagnosis, various manufacturers.
* Digital breast tomosynthesis (DBT), FDA Approved for breast screening and diagnosis, various manufacturers.

OBJECTIVES:

* Primary: To establish a library of cases for use in future SoftVue™ research studies, user training, and marketing.
* Secondary: Determine the frequency and severity of adverse events (AEs) to further evaluate the safety of SoftVue.

ENDPOINTS:

From multiple clinical sites whichever comes first:

* Up to 17,500 total enrolled subjects
* Up to 105 total breast cancer cases detected at program entry screening
* At least 35 total discordant breast cancer cases, where FFDM is negative or benign (BI-RADS 1 or 2) but SV is incomplete (BIRADS 0) and diagnostic imaging workup of SV findings leads to breast biopsy with malignant pathology

SITES:

At least six (≥ 6) qualified clinical sites in the United States

* MQSA Certified
* Digital Breast Tomosynthesis Screening Program Implemented
* Academic, Community Hospital, or Private Practice Setting

PROJECT DESIGN AND PROCEDURES:

* Potential participants will be recruited from the group of women presenting for their annual breast imaging exams at multiple clinical sites utilizing 3D DBT and 2D FFDM (non-synthesized) for routine screening.
* Asymptomatic women with heterogeneously or extremely dense breast parenchyma (BI-RADS composition c or d), based on visual assessment of FFDM by trained site personnel, will be invited to consider volunteering to participate in the case collection program.
* All participants will complete the same routine screening FFDM + DBT evaluation for which they originally reported to the clinic, with a complete set of 2D views and 3D views.
* Eligible patients will receive SV as an adjunct to FFDM + DBT.
* A single Investigator (radiologist) at each site will perform sequential review of the same subjects FFDM, DBT, and SV images.
* FFDM will be evaluated for final parenchymal density (BI-RADS a through d) and then each exam will be assigned to one of 3 BI-RADS assessment categories (0, 1, 2) by the radiologist.
* Abnormal findings will be indicated by a BI-RADS assessment category of 0 (Incomplete)and will undergo diagnostic imaging evaluations consistent with universally accepted standards of care.
* All evaluation results, diagnosis and treatment outcomes will be recorded.
* Normal findings will be indicated by BI-RADS assessment categories of 1 or 2 (Negative or Benign) which will be associated with a management recommendation to resume routine screening in one year, unless symptoms or signs of breast cancer develop in the interim.
* All participants who are not diagnosed with breast cancer as a direct result of the program entry examinations, incidental evaluations, or interval symptoms, will return to the site in 12 months for their next annual screening exam, the results and outcome of which will be recorded.
* Cancer status for all participants will be surveyed from program entry until and including the completion of recommended follow-up.
* A case will be determined cancer negative if the participant has no findings suspicious for cancer throughout the interval between program entry and completion of annual follow-up.
* A case will be determined cancer positive if a pathological evaluation confirms a breast cancer diagnosis during the interval between program entry and completion of annual follow-up.

STATISTICAL ANALYSIS:

* Demographic characteristics (age, race, and ethnicity) and other baseline characteristics (e.g., project arm, project site, breast density, lesion-specific characteristics) will be tabulated for all participants.
* A flow diagram or table will illustrate patient disposition ("accountability of patient cohort") including reasons for ineligibility and/or unevaluability.
* Safety will be summarized for all enrolled women. With the exception of anticipated events, adverse events (AEs) and serious adverse events (SAEs), occurring from the time of enrollment (SoftVue) and for 24 hours following the conclusion of the SoftVue exam, will be recorded.
* A separate statistical plan will be developed for any future analysis that includes justification of sample size and, if applicable to the requirements of FDAAA 801, will be registered separately in order to share the results.

Delphinus SoftVue Prospective Case Collection - ARM 1

ARM 1: A Prospective, Multicenter, Multi-arm, Clinical Case Collection Program to Acquire Breast Image Data and Establish an Image Library of Exams for Use in Future Research Studies, Training, and Product Development Efforts.

Non-Cancer cases, confirmed by normal or negative mammographic breast imaging (FFDM or DBT), or breast biopsy with benign pathology, after at least 365 days of follow-up

Cancer cases, confirmed by breast biopsy with malignant pathology, within 365 days of follow-up

Delphinus Medical Technologies, Inc.

Immune System Diseases

Hypersensitivity

Women who have no signs or symptoms of breast cancer who have \> 50% parenchymal density on mammography.

After density \> 50% is confirmed by routine digital screening mammography, ABUS will be performed.

Automated Breast Ultrasound (ABUS) as an adjunct to digital screening mammography

Rachel F Brem, MD

Hypothesis: A higher sensitivity to breast cancer detection can be achieved in women with dense breast tissue by performing and reviewing results of Automated Breast Ultrasound (ABUS) and Digital X-Ray Mammography (XRM) together as part of routine screening compared to performing and reviewing results of XRM alone.

Primary Objective: For the cohort of asymptomatic women who have dense breast tissue, calculate the sensitivity of Digital X-Ray Mammography (XRM) and ABUS together as a breast cancer screening modality and compare it to that of XRM alone.

Secondary Objective: For the cohort of asymptomatic women who have dense breast tissue, evaluate the specificity of XRM and ABUS together compared to that of XRM alone; Calculate the negative predictive value (NPV) and positive predictive value (PPV) for XRM and ABUS.

Endpoint: Breast cancers detected by radiologists in the clinical screening setting and confirmed by pathology.

Study Design: This is a prospective matched-pair clinical study enrolling more than 20,000 women with parenchymal density \> 50% on digital x-ray mammography (XRM). Participants will receive ABUS as an adjunct to XRM. Any abnormal findings, from either XRM or ABUS, will receive appropriate management action consistent with accepted medical standards of care. All evaluation results, diagnosis and treatment outcomes will be recorded. Participants will be followed for one year and those who are not diagnosed with breast cancer at enrollment or during the follow-up interval must undergo an annual mammogram at study completion, the outcome of which will be recorded.

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:

1. 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.
2. 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.
3. 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.
4. 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:

1. 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.
2. 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.

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.

A Prospective Multicenter Matched-pair Clinical Study to Evaluate the Sensitivity and Specificity of ABUS and Digital X-Ray Mammography (XRM) Together as a Breast Cancer Screening Method Compared to XRM Alone in Women With >50% Parenchymal Density.

U-Systems, Inc.

Non-Interventional: Women presenting to enrollment sites for diagnostic examinations of symptoms or imaging findings, as recommended by a physician, and assigned BI-RADS category 4 or 5 (biopsy indicated).

Only standard care procedures will be performed for clinical intervention and diagnostic purposes.

Non-Interventional

Bilateral breast ultrasound images will be captured, but not clinically evaluated for diagnostic purposes by a physician.

The SoftVue™ is a whole breast ultrasound system with an automated scanning curvilinear ring-array transducer that employs UST. It is currently cleared under FDA 510(k) K123209 and K142517 for use as both a B-mode ultrasonic breast imaging system and color imaging of transmission data (sound speed and attenuation). SoftVue™ is not intended to be used as a replacement for screening mammography.

SoftVue uses non-ionizing ultrasound energy to generate tomographic image volumes of the whole breast. While the patient lays prone on a padded table with one breast comfortably submerged in a bath of warm water, a ring-shaped transducer, 22 cm in diameter, encircles the breast and pulses low-frequency sound waves through the water and into the breast tissue. More than 2000 elements in the curvilinear transducer's 360 degree array emit and receive ultrasound signals to analyze echoes from the breast anatomy in all directions, from the chest wall to the nipple. Not only does SoftVue capture data from the reflection of the sound waves off of tissue boundaries and structures within the breast, but because the transducer surrounds the whole breast, SoftVue also captures signals that are transmitted through the breast. This additional transmission data enhances the visualization of the anatomic structure of the breast tissue and is not currently available in any other commercially marketed breast ultrasound device.

This prospective, multicenter, multi-arm, clinical case collection program is IRB-approved and will be conducted in compliance with Good Clinical Practice, the Declaration of Helsinki and all applicable regulatory requirements. Arm 2 aims to collectively enroll up to 1,000 women at a total of up to 8 clinical sites. The design of Arm 2 in this protocol is strictly limited to case collection and is non-interventional; any investigational and/or statistical plans for future analyses will be prepared and registered separately, if they are applicable to the requirements of FDAAA 801.

Arm 2 is limited to the cohort of diagnostic female patients of any breast density composition category, who have been recommended for a breast biopsy (BI-RADS 4 or 5) after diagnostic imaging, or who have confirmed imaging findings. Matched sets of diagnostic imaging and SV exams, from the same patient, demographic information, and clinical outcome data, will be collected during diagnostic workup. Ultrasound characteristics for all types of lesions, whether they are benign or malignant, will be collected as well as objective and subjective breast density composition data. Ultrasound image data may be acquired with modified SoftVue devices, which have passed safety and quality evaluations per Delphinus' quality management system (QMS) and satisfy design change control standards, at select clinical sites in accordance with 21 CFR 812.2 (b), as a routine part of feasibility, validation, and verification testing for engineering and product development purposes.

The exams and clinical data accumulated in this prospective case collection (PCC) protocol will populate a database from which future investigations may be designed for peer reviewed publication, development of user training curricula, building teaching case, and creating new marketing materials for SoftVue.

MEDICAL DEVICES:

* SoftVue™ (SV) automated whole breast ultrasound system, 510(k) Cleared for B-Mode ultrasound breast imaging, manufactured by Delphinus Medical Technologies.
* SoftVue™ with device modifications (software, hardware, user-interface), safety-tested for human use to complete feasibility, verification, and validation testing as a routine part of product development and performed in accordance with FDA 21 CFR 812.2 (b), manufactured by Delphinus Medical Technologies.
* Full-field digital mammography (FFDM), FDA Approved for breast screening and diagnosis, various manufacturers. (If clinically indicated)
* Digital breast tomosynthesis (DBT), FDA Approved for breast screening and diagnosis, various manufacturers.
* Handheld Ultrasound (HHUS), FDA-Cleared for diagnostic breast imaging, various manufacturers. (If clinically indicated)
* Other diagnostic tests and medical device examinations of the breast, including, but not limited to MRI, BSGI, PET, biopsy, and elastography, on the order of a licensed physician, when clinically indicated.

OBJECTIVES:

* Primary: To establish a library of cases for use in future SoftVue™ research studies, user training, and marketing.
* Secondary: Determine the frequency and severity of adverse events (AEs) to further evaluate the safety of SoftVue.

ENDPOINTS:

From multiple clinical sites whichever comes first:

• Up to 1,000 total enrolled subjects

SITES:

At least six (≥ 6) qualified clinical sites in the United States

* MQSA Certified
* Digital Breast Tomosynthesis Screening Program Implemented
* Academic, Community Hospital, or Private Practice Setting

PROJECT DESIGN AND PROCEDURES:

* Potential participants will be recruited from the group of women presenting for diagnostic evaluation or biopsy at multiple clinical sites.
* All participants will complete the same standard care diagnostic evaluations that were recommended by a physician
* Eligible patients will receive a SV scan at the time of their scheduled diagnostic appointments, preferably prior to biopsy
* Investigators at the sites will compare SV images to the accompanying diagnostic images and pathology results
* No clinical SV interpretation will be performed and no clinical interventions will be made or changed based on SV images
* All evaluation results, diagnosis and treatment outcomes will be recorded
* Cancer status for all participants will be surveyed from program entry until and including the completion of physician recommended diagnostic workup
* A case will be determined cancer negative if the participant has non-malignant breast biopsy findings or confirmed non-suspicious diagnostic breast imaging findings
* A case will be determined cancer positive if a pathological evaluation confirms a breast cancer diagnosis (malignancy)

STATISTICAL ANALYSIS:

* Demographic characteristics (age, race, and ethnicity) and other baseline characteristics (e.g., project arm, project site, breast density, lesion-specific characteristics) will be tabulated for all participants.
* A flow diagram or table will illustrate patient disposition ("accountability of patient cohort") including reasons for ineligibility and/or unevaluability.
* Safety will be summarized for all enrolled women. With the exception of anticipated events, adverse events (AEs) and serious adverse events (SAEs), occurring from the time of enrollment (SoftVue) and for 24 hours following the conclusion of the SoftVue exam, will be recorded.
* A separate statistical plan will be developed for any future analysis that includes justification of sample size and, if applicable to the requirements of FDAAA 801, will be registered separately in order to share the results.

Delphinus SoftVue Prospective Case Collection - ARM 2

ARM 2: A Prospective, Multicenter, Multi-arm, Clinical Case Collection Program to Acquire Breast Image Data and Establish an Image Library of Exams for Use in Future Research Studies, Training, and Product Development Efforts.

Non-Cancer cases, confirmed by normal or negative breast imaging findings or concordant breast biopsy with benign pathology.

Cancer cases, confirmed by breast biopsy with malignant pathology

Automated Breast Ultrasound (ABUS) as an adjunct to digital screening mammography.

Automated Breast Ultrasound (ABUS)

Maryellen Giger, Ph.D.

To determine the impact on Interpreting Physician performance in detecting breast cancer, as defined by the area under the Receiver Operating Characteristic Curve (ROC), when Automated Breast Ultrasound (ABUS) and screening mammography (XRM) are combined, compared to screening mammography alone in asymptomatic women with \>50% parenchymal density and a screening mammogram assigned a BI-RADS Assessment Category 1 (negative) or 2 (normal with benign findings).

The effect of the improved Reader performance is illustrated by plotting the ROC curves for XRM alone and XRM+ABUS. If Reader performance improves with the addition of ABUS to the XRM, the area under the curve (AUC) for XRM+ABUS (AUCXRM+ABUS) will be greater than the area under the curve for XRM Alone (AUCXRM Alone). This difference is represented as ∆AUCABUS. The null and alternative hypotheses can be formally expressed as follows:

H0: ∆AUCABUS = 0, AUCXRM+ABUS = AUCXRM Alone The null hypothesis is that Reader performance will be unchanged with the addition of ABUS to a screening mammogram assigned a BI-RADS Assessment Category of 1 or 2.

HA: ∆AUCABUS ≠ 0, AUCXRM+ABUS ≠ AUCXRM Alone The alternative hypothesis is that Reader performance will be changed with the addition of ABUS to a screening mammogram assigned a BI-RADS Assessment Category of 1 or 2. A statistically significant change will be considered equivalent to a statistically significant improvement if the estimated value of AUCXRM+ABUS is greater than that of AUCXRM Alone with statistical significance at an alpha level of .05 for a two-sided test.

The Clinical Retrospective Reader Study is an observational case-controlled, multi-reader multi-case Receiver Operating Characteristic (ROC) study involving approximately 16 Interpreting Physicians (Readers) and approximately 200 breast screening cases which will be reviewed and of those, 164 breast screening cases will be included in the primary data analysis. All primary data analysis cases will consist of screening mammogram and Automated Breast Ultrasound image readings from the same asymptomatic females with \>50% parenchymal density for whom the screening mammogram was assigned a BI-RADS Assessment Category 1 (negative) or 2 (normal with benign findings).

The Readers will review a total of 200 cases: the Non-Cancer Case Set, the Cancer Case Set, and additional Control and Supplemental Case Sets. These cases will be randomized during the reading session so each Reader will review the entire Case Set in a unique order.

The primary Receiver Operating Characteristic analysis will be performed on the Readers' Likelihood of Malignancy (LOM) ratings from their initial review of the screening mammogram alone and their final review of the screening mammogram and Automated Breast Ultrasound for the Non-Cancer Case Set and Cancer Case Set.

CRRS-4 Pivotal Somo•v™ ABUS ROC Reader Observer Study

To Determine the Impact on Reader Performance, as Defined by the Area Under the Receiver Operating Characteristic Curve, When Automated Breast Ultrasound and a Screening Mammogram Are Combined, Compared to a Screening Mammogram Alone in Asymptomatic Women With >50% Parenchymal Density and a Screening Mammogram Assigned a BI-RADS Assessment Category 1 (Negative) or 2 (Normal With Benign Findings).

To determine the impact on Interpreting Physician (Reader) Performance in detecting breast cancer, as defined by the area under the Receiver Operating Characteristic (ROC) Curve (AUC), when ABUS and XRM are combined (XRM+ABUS), compared to XRM Alone in asymptomatic women with \>50% parenchymal density (BI-RADS Composition/Density rating of 3 or 4) and a screening mammogram assigned a BI-RADS Assessment Category 1 (negative) or 2 (normal with benign findings).

Reader sensitivity and specificity when XRM+ABUS are combined compared to XRM Alone for two different combinations of cut points.

Participants undergo HHUS and ABUS in no required order over 1 hour.

Ultrasonography

Automated Breast Ultrasound

Lisa Zorn, MD

This clinical trial evaluates automated breast ultrasound (ABUS) and handheld ultrasound (HHUS) for the screening of women who have undergone breast reconstruction after breast cancer. Ultrasounds use high-frequency sound waves to create pictures of internal organs and tissues. ABUS has been found to be equal to HHUS for whole breast screening, but no data exist on its use for screening of reconstructed patients. This clinical trial evaluates the feasibility of using ABUS versus HHUS to screen women who have undergone reconstruction.

PRIMARY OBJECTIVE:

I. To show that ABUS reduces artifact compared to HHUS in terms of detection of the residual tissue in reconstructed nipple sparing mastectomy (NSM) and skin sparing mastectomy (SSM) patients.

SECONDARY OBJECTIVES:

I. To evaluate both the performance and interpretation times for ABUS and HHUS so that these factors can be considered when scheduling patients and for ease of implementation into practice.

II. A short survey will be administered immediately after both ultrasounds performed to enrolled patients to assess their experience with HHUS and ABUS, specifically addressing their perceived comfort level on a numerical scale and if they would be interested in obtaining subsequent annual screening HHUS or ABUS.

EXPLORATORY OBJECTIVE:

I. The appearance of native and reconstructed anatomy on ABUS and HHUS will be studied.

OUTLINE:

Participants undergo HHUS and ABUS in no required order over 1 hour.

Participants with ultrasound results indicating Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 (suspicious and needs biopsy) undergo biopsy within 30 days.

A Study to Compare the Effectiveness of Two Types of Ultrasound Technologies in Women Who Have Had Breast Cancer

Feasibility of Automated Breast Ultrasound (ABUS) Versus Handheld Ultrasound (HHUS) for Breast Cancer Surveillance in Women With Nipple Sparing or Skin Sparing Mastectomy With Reconstruction

This is a binary endpoint. The rate of artifact will be compared between handheld and automated scanning using McNemar test.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Delphinus SoftVue Prospective Case Collection - ARM 1	NCT03257839	Breast Neoplasm...	Routine Full-Fi... Routine Digital... Automated Whole...	18 Years -	Delphinus Medical Technologies, Inc.
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.	NCT00816530	Breast Cancer	Automated Breas...	25 Years -	U-Systems, Inc.
Delphinus SoftVue Prospective Case Collection - ARM 2	NCT02977247	Breast Neoplasm...	Non-Interventio... Automated Whole...	18 Years -	Delphinus Medical Technologies, Inc.
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.	NCT00816530	Breast Cancer	Automated Breas...	25 Years -	U-Systems, Inc.
CRRS-4 Pivotal Somo•v™ ABUS ROC Reader Observer Study	NCT01424956	Breast Cancer	Automated Breas...	-	U-Systems, Inc.
A Study to Compare the Effectiveness of Two Types of Ultrasound Technologies in Women Who Have Had Breast Cancer	NCT05408260	Malignant Breas...	Ultrasonography Automated Breas...	18 Years -	Thomas Jefferson University

Spots Global Cancer Trial Database for automated breast ultrasound