Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
NCT ID: NCT03233191
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE3
108508 participants
INTERVENTIONAL
2017-09-28
2030-12-31
Brief Summary
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Detailed Description
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I. To compare the proportions of participants in the tomosynthesis mammography (TM) and digital mammography (DM) study arms experiencing the occurrence of an ?advanced? breast cancer at any time during a period of 4.5 years from randomization, including the period of active screening and a period of clinical follow-up after the last screen (T4).
SECONDARY OBJECTIVES:
I. To assess the potential effect of age, menopausal and hormonal status, breast density, and family cancer history on the primary endpoint difference between the two arms.
II. To compare the diagnostic performance of TM and DM, as measured by the area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).
III. To compare the recall rates and biopsy rates for TM versus DM, with subset analyses by the same variables as listed in aim II.
IV. To compare the rate of interval cancers for TM and DM and to assess the mechanism of diagnosis for these interval cancers with categorization by symptomatic versus (vs) asymptomatic, and how detected: diagnosed via physical examination, mammography, ultrasound (US), magnetic resonance imaging (MRI) or other technologies.
V. To examine the correlation between Breast Imaging Reporting and Data System (BIRADS) imaging features and histologic and genetic features, such as invasive ductal and invasive lobular histology, high grade, high stage at diagnosis, and aggressive genetic subtypes.
VI. To assess different combinations of TM and synthesized 2 dimensional (2D) or DM in reader studies to assist in determining the optimum balance between diagnostic performance, radiation exposure and technique.
VII. To estimate and compare breast-cancer-specific mortality between the two study arms.
VIII. To estimate and compare the prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) low, medium or high proliferation via PAM50 proliferation signatures, and p53 mutant-like or wild-type-like according to a validated p53 dependent signature in the two arms, overall and stratified on whether cancers were detected through screening or as interval cancers, and whether cancers were invasive or in situ.
IX. To classify histologically malignant (true positive cases) and benign lesions (false positive cases) as normal-like or tumor-like using the PAM50 gene expression assay subtype (luminal A, luminal B, HER2, basal-like,), and low, medium, or high proliferation according to PAM50 proliferation signatures, and p53 mutant-like or wild-type-like according to a validated p53-dependent signature.
X. To assess the agreement between local and expert study pathologists for all breast lesions (benign and malignant) biopsied during the 4.5 years of screening with TM or DM.
XI. To create a blood and buccal cell biobank for future biomarker and genetic testing.
XII. To compare health care utilization (including cancer care received) and cost of an episode of breast cancer screening by TM versus DM, overall and within subsets.
XIII. To implement a centralized quality control (QC) monitoring program for both 2D digital mammography (DM) and tomosynthesis (TM), which provides rapid feedback on image quality, using quantitative tools, taking advantage of the automated analysis of digital images.
XIV. To assess temporal and site-to site variations in image quality, breast radiation dose, and other quality control parameters in TM vs. DM.
XV. To refine and implement task-based measures of image quality to assess the effects of technical parameters, including machine type, and detector spatial and contrast resolution on measures of diagnostic accuracy for TM.
XVI. To evaluate which QC tests are useful for determination of image quality and those that are predictive of device failure, in order to recommend an optimal QC program for TM.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients undergo bilateral screening DM with standard craniocaudal (CC) and mediolateral oblique (MLO) views at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.
ARM B: Patients undergo manufacturer-defined screening TM at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.
After completion of study, patients are followed up for at least 3- 8 years after study entry.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
SCREENING
NONE
Study Groups
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Arm A (digital mammography)
Patients undergo bilateral screening DM with standard CC and MLO views at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.
Digital Mammography
Undergo DM
Laboratory Biomarker Analysis
Correlative studies
Arm B (digital tomosynthesis mammography)
Patients undergo manufacturer-defined screening TM at baseline, 12, 24, 36, and 48 months if pre-menopausal or at baseline, 24, and 48 months if post-menopausal.
Digital Tomosynthesis Mammography
Undergo TM
Laboratory Biomarker Analysis
Correlative studies
Interventions
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Digital Mammography
Undergo DM
Digital Tomosynthesis Mammography
Undergo TM
Laboratory Biomarker Analysis
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must be scheduled for, or have intent to schedule, a screening mammogram
* Patients must be able to tolerate digital breast tomosynthesis and full-field digital mammographic imaging required by protocol.
* Patients must be willing and able to provide a written informed consent
* Patients must not have symptoms or signs of benign or malignant breast disease (eg, nipple discharge, breast lump) warranting a diagnostic rather than a screening mammogram, and/or other imaging studies (eg, sonogram); patients with breast pain are eligible as long as other criteria are met
* Patients must not have had a screening mammogram within the last 11 months prior to date of randomization
* Patients must not have previous personal history of breast cancer including ductal carcinoma in situ
* Patients must not have breast enhancements (e.g., implants or injections)
* ANNUAL SCREENING REGIMEN ELIGIBILITY CHECK
* To be eligible for inclusion in the annual screening regimen one of the following three conditions must be met in addition to the eligibility criteria above:
* Patients are pre-menopausal; OR
* Post-menopausal aged 45-69 with any of the following three risks factors:
* Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
* Family history of breast cancer (first degree relative with breast cancer), or, positive genetic testing for any deleterious genes that indicate an increased risk for breast cancer, or
* Currently on hormone therapy; OR
* Post-menopausal ages 70-74 with either of the following two risk factors:
* Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or
* Currently on hormone therapy
* Postmenopausal women are defined as those with their last menstrual period more than 12 months prior to study entry; for the purpose of defining menopausal status for women who have had surgical cessation of their periods, women who no longer have menses due to hysterectomy and oophorectomy will be considered postmenopausal; women who no longer have menses due to hysterectomy without oophorectomy will be considered premenopausal until age 52 and postmenopausal thereafter
* All other postmenopausal women are eligible for inclusion in the biennial screening regimen
* For those women who cannot be assigned to annual or biennial screening at the time of study entry and randomization because they are postmenopausal, have no family history or known deleterious breast cancer mutation, are not on hormone therapy AND have not had a prior mammogram, breast density will be determined by the radiologist?s recording of it at the time of interpretation of the first study screening examination, either DM or TM; for those who are randomized to TM, radiologists will assign BI-RADS density through review of the DM or synthetic DM portion of the TM examination; such women cannot be part of the planned stratification by screening frequency and are expected to represent far less than 1% of the Tomosynthesis Mammographic Imaging Screening Trial (TMIST) population
* Breast density will be determined by prior mammography reports, when available; all other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report
45 Years
74 Years
FEMALE
Yes
Sponsors
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National Cancer Institute (NCI)
NIH
Canadian Cancer Trials Group (CCTG)
UNKNOWN
ECOG-ACRIN Cancer Research Group
NETWORK
Responsible Party
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Principal Investigators
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Etta Pisano
Role: PRINCIPAL_INVESTIGATOR
ECOG-ACRIN Cancer Research Group
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Mobile Infirmary Medical Center
Mobile, Alabama, United States
Banner-University Medical Center Phoenix
Phoenix, Arizona, United States
University of Arizona College of Medicine Phoenix
Phoenix, Arizona, United States
Valleywise Comprehensive Health Center - Phoenix
Phoenix, Arizona, United States
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Scottsdale Medical Imaging Limited
Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Kern Radiology Medical Group Inc
Bakersfield, California, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Kaiser Permanente-Modesto
Modesto, California, United States
Zuckerberg San Francisco General Hospital
San Francisco, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Penrose-Saint Francis Healthcare
Colorado Springs, Colorado, United States
The Women's Imaging Center
Denver, Colorado, United States
Radiology Imaging Associates
Englewood, Colorado, United States
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado, United States
UCHealth Lone Tree Health Center
Lone Tree, Colorado, United States
Helen F Graham Cancer Center
Newark, Delaware, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
University of Florida Health Science Center - Jacksonville
Jacksonville, Florida, United States
Northside Hospital
Atlanta, Georgia, United States
Northeast Georgia Medical Center Braselton
Braselton, Georgia, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, United States
Queen's Medical Center
Honolulu, Hawaii, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, United States
Bromenn Lifecare Center
Bloomington, Illinois, United States
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, United States
Carle at The Riverfront
Danville, Illinois, United States
Carle on Fairchild
Danville, Illinois, United States
Decatur Memorial Hospital
Decatur, Illinois, United States
Carle Hoopeston Regional Health Center
Hoopeston, Illinois, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, United States
Bromenn Regional Medical Center
Normal, Illinois, United States
Carle Cancer Center
Urbana, Illinois, United States
Saint Mary Medical Center
Hobart, Indiana, United States
Indiana University/Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
The Community Hospital
Munster, Indiana, United States
Women's Diagnostic Center - Munster
Munster, Indiana, United States
Northwest Cancer Center - Valparaiso
Valparaiso, Indiana, United States
Mercy Medical Center - Des Moines
Des Moines, Iowa, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States
Owensboro Health Mitchell Memorial Cancer Center
Owensboro, Kentucky, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, United States
Woman's Hospital
Baton Rouge, Louisiana, United States
Tulane University School of Medicine
New Orleans, Louisiana, United States
University Medical Center New Orleans
New Orleans, Louisiana, United States
Ochsner LSU Health Saint Mary's Medical Center
Shreveport, Louisiana, United States
LSU Health Sciences Center at Shreveport
Shreveport, Louisiana, United States
Kaiser Permanente - Kensington Medical Center
Kensington, Maryland, United States
Boston Medical Center
Boston, Massachusetts, United States
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Bronson Battle Creek
Battle Creek, Michigan, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Henry Ford Hospital
Detroit, Michigan, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
Grand Rapids, Michigan, United States
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, United States
Essentia Health Cancer Center
Duluth, Minnesota, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, United States
Regions Hospital
Saint Paul, Minnesota, United States
Sanford Thief River Falls Medical Center
Thief River Falls, Minnesota, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, United States
Baptist Memorial Hospital and Cancer Center-Desoto
Southhaven, Mississippi, United States
Carson Tahoe Regional Medical Center
Carson City, Nevada, United States
Hunterdon Medical Center
Flemington, New Jersey, United States
Saint Peter's University Hospital
New Brunswick, New Jersey, United States
Riverview Medical Center/Booker Cancer Center
Red Bank, New Jersey, United States
Sidney Kimmel Cancer Center Washington Township
Sewell, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
Arnot Ogden Medical Center/Falck Cancer Center
Elmira, New York, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
University of Rochester
Rochester, New York, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
University of North Carolina-Hillsborough Campus
Hillsborough, North Carolina, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, United States
Southpointe-Sanford Medical Center Fargo
Fargo, North Dakota, United States
Cleveland Clinic Cancer Center Beachwood
Beachwood, Ohio, United States
Aultman Health Foundation
Canton, Ohio, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Easton Hospital
Easton, Pennsylvania, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
Wexford Health and Wellness Pavilion
Wexford, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Prisma Health Richland Hospital
Columbia, South Carolina, United States
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina, United States
MUSC Health East Cooper
Mt. Pleasant, South Carolina, United States
Spartanburg Medical Center
Spartanburg, South Carolina, United States
Spartanburg Medical Center - Mary Black Campus
Spartanburg, South Carolina, United States
University of Tennessee - Knoxville
Knoxville, Tennessee, United States
Baptist Memorial Hospital and Cancer Center-Memphis
Memphis, Tennessee, United States
Baptist Memorial Hospital for Women
Memphis, Tennessee, United States
Vanderbilt Breast Center at One Hundred Oaks
Nashville, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
Memorial Hermann Texas Medical Center
Houston, Texas, United States
Memorial Hermann Imaging Center - Upper Kirby
Houston, Texas, United States
University Hospital
San Antonio, Texas, United States
University of Virginia Cancer Center
Charlottesville, Virginia, United States
Bon Secours Westchester Emergency Center
Midlothian, Virginia, United States
Sentara Leigh Hospital
Norfolk, Virginia, United States
Sentara Norfolk General Hospital
Norfolk, Virginia, United States
Sentara Princess Anne Hospital
Virginia Beach, Virginia, United States
Swedish Medical Center-First Hill
Seattle, Washington, United States
West Virginia University Healthcare
Morgantown, West Virginia, United States
ThedaCare Regional Cancer Center
Appleton, Wisconsin, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, United States
ProHealth D N Greenwald Center
Mukwonago, Wisconsin, United States
ProHealth Oconomowoc Memorial Hospital
Oconomowoc, Wisconsin, United States
Essentia Health Saint Mary's Hospital - Superior
Superior, Wisconsin, United States
UW Cancer Center at ProHealth Care
Waukesha, Wisconsin, United States
CERIM
Buenos Aires, , Argentina
BCCA-Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Saint Joseph's Health Care London
London, Ontario, Canada
Ottawa Hospital and Cancer Center-General Campus
Ottawa, Ontario, Canada
Odette Cancer Centre- Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
Hopital Du Sacre-Coeur de Montreal
Montreal, Quebec, Canada
CHU de Quebec-Hopital du Saint-Sacrement (HSS)
Québec, Quebec, Canada
Hospital Sotero Del Rio
Puente Alto, Santiago Metropolitan, Chile
Ospedale Ca Foncello di Treviso - ULSS 2 Marca Trevigiana
Treviso, , Italy
Oncosalud S.A.C.
Lima, , Peru
San Juan City Hospital
San Juan, , Puerto Rico
National Cancer Center-Korea
Goyang-si, Gyeonggi-do, South Korea
Parc Tauli Sabadell Hospital Universitari
Sabadell, Barcelona, Spain
Taipei Veterans General Hospital
Taipai, , Taiwan
Chiang Mai University
Chiang Mai, Muang, Thailand
Countries
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References
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Maki AK, Mawdsley GE, Mainprize JG, Pisano ED, Shen SZ, Alonzo-Proulx O, Yaffe MJ. Quality control for digital tomosynthesis in the ECOG-ACRIN EA1151 TMIST trial. Med Phys. 2023 Dec;50(12):7441-7461. doi: 10.1002/mp.16786. Epub 2023 Oct 13.
Other Identifiers
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NCI-2017-01111
Identifier Type: REGISTRY
Identifier Source: secondary_id
EA1151
Identifier Type: OTHER
Identifier Source: secondary_id
EA1151
Identifier Type: OTHER
Identifier Source: secondary_id
EA1151
Identifier Type: OTHER
Identifier Source: secondary_id
EA1151
Identifier Type: -
Identifier Source: org_study_id