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AzTrials

Breast ScreeningPhase 3NCT03233191

Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer

A Phase 3 study testing Digital Mammography, Digital Tomosynthesis Mammography and Laboratory Biomarker Analysis in people with Breast Screening, run by ECOG-ACRIN Cancer Research Group at 149 sites in 11 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This randomized phase III trial studies digital tomosynthesis mammography and digital mammography in screening patients for breast cancer. Screening for breast cancer with tomosynthesis mammography may be superior to digital mammography for breast cancer screening and may help reduce the need for additional imaging or… Read more about this study

Who is it for?
Ages 45 to 74 years, women onlyHealthy volunteers can take part
Conditions the study is for
Breast Screening
What is being tested?
Digital Mammography, Digital Tomosynthesis Mammography and Laboratory Biomarker Analysis
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108,508 participants
Where
149 sitesin 11 countries
Study dates
28 Sep 2017to 31 Dec 2029
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 45 to 74 years
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Women of childbearing potential must not be known to be pregnant or lactating
  • 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
Show all 22Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

149 sites in 11 countries.

149 sites in 11 countries

United States133 sites

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • Trinity Health Saint Joseph Mercy Hospital Ann Arbor

    Ann Arbor, Michigan, 48106

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • ThedaCare Regional Cancer Center

    Appleton, Wisconsin, 54911

  • Northside Hospital

    Atlanta, Georgia, 30342

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Kern Radiology Medical Group Inc

    Bakersfield, California, 93306

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • Woman's Hospital

    Baton Rouge, Louisiana, 70817

  • Bronson Battle Creek

    Battle Creek, Michigan, 49017

  • Cleveland Clinic Cancer Center Beachwood

    Beachwood, Ohio, 44122

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Sanford Bismarck Medical Center

    Bismarck, North Dakota, 58501

  • Bromenn Lifecare Center

    Bloomington, Illinois, 61701

  • Saint Alphonsus Cancer Care Center-Boise

    Boise, Idaho, 83706

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • Northeast Georgia Medical Center Braselton

    Braselton, Georgia, 30517

  • Aultman Health Foundation

    Canton, Ohio, 44710

  • Carson Tahoe Regional Medical Center

    Carson City, Nevada, 89703

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • John H Stroger Jr Hospital of Cook County

    Chicago, Illinois, 60612

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Penrose-Saint Francis Healthcare

    Colorado Springs, Colorado, 80907

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Carle on Fairchild

    Danville, Illinois, 61832

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • The Women's Imaging Center

    Denver, Colorado, 80209

  • Mercy Medical Center - Des Moines

    Des Moines, Iowa, 50314

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Essentia Health Cancer Center

    Duluth, Minnesota, 55805

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Easton Hospital

    Easton, Pennsylvania, 18042

  • Arnot Ogden Medical Center/Falck Cancer Center

    Elmira, New York, 14905

  • Radiology Imaging Associates

    Englewood, Colorado, 80112

  • Southpointe-Sanford Medical Center Fargo

    Fargo, North Dakota, 58103

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • Hunterdon Medical Center

    Flemington, New Jersey, 08822

  • Corewell Health Grand Rapids Hospitals - Butterworth Hospital

    Grand Rapids, Michigan, 49503

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • UCHealth Highlands Ranch Hospital

    Highlands Ranch, Colorado, 80129

  • University of North Carolina-Hillsborough Campus

    Hillsborough, North Carolina, 27278

  • Saint Mary Medical Center

    Hobart, Indiana, 46342

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Carle Hoopeston Regional Health Center

    Hoopeston, Illinois, 60942

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Hermann Texas Medical Center

    Houston, Texas, 77030

  • Memorial Hermann Imaging Center - Upper Kirby

    Houston, Texas, 77098

  • Indiana University/Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Florida Health Science Center - Jacksonville

    Jacksonville, Florida, 32209

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • Kaiser Permanente - Kensington Medical Center

    Kensington, Maryland, 20895

  • University of Tennessee - Knoxville

    Knoxville, Tennessee, 37920

  • Gundersen Lutheran Medical Center

    La Crosse, Wisconsin, 54601

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • UCHealth Lone Tree Health Center

    Lone Tree, Colorado, 80124

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Baptist Memorial Hospital and Cancer Center-Memphis

    Memphis, Tennessee, 38120

  • Baptist Memorial Hospital for Women

    Memphis, Tennessee, 38120

  • Bon Secours Westchester Emergency Center

    Midlothian, Virginia, 23113

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Mobile Infirmary Medical Center

    Mobile, Alabama, 36607

  • Kaiser Permanente-Modesto

    Modesto, California, 95356

  • West Virginia University Healthcare

    Morgantown, West Virginia, 26506

  • MUSC Health East Cooper

    Mt. Pleasant, South Carolina, 29464

  • ProHealth D N Greenwald Center

    Mukwonago, Wisconsin, 53149

  • The Community Hospital

    Munster, Indiana, 46321

  • Women's Diagnostic Center - Munster

    Munster, Indiana, 46321

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Saint Peter's University Hospital

    New Brunswick, New Jersey, 08901

  • Tulane University School of Medicine

    New Orleans, Louisiana, 70112

  • University Medical Center New Orleans

    New Orleans, Louisiana, 70112

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Sentara Leigh Hospital

    Norfolk, Virginia, 23502

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Bromenn Regional Medical Center

    Normal, Illinois, 61761

  • ProHealth Oconomowoc Memorial Hospital

    Oconomowoc, Wisconsin, 53066

  • Owensboro Health Mitchell Memorial Cancer Center

    Owensboro, Kentucky, 42303

  • Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19107

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Banner-University Medical Center Phoenix

    Phoenix, Arizona, 85006

  • University of Arizona College of Medicine Phoenix

    Phoenix, Arizona, 85006

  • Valleywise Comprehensive Health Center - Phoenix

    Phoenix, Arizona, 85008

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • Riverview Medical Center/Booker Cancer Center

    Red Bank, New Jersey, 07701

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • University of Rochester

    Rochester, New York, 14642

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • University Hospital

    San Antonio, Texas, 78229

  • Zuckerberg San Francisco General Hospital

    San Francisco, California, 94110

  • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

    Savannah, Georgia, 31405

  • Scottsdale Medical Imaging Limited

    Scottsdale, Arizona, 85258

  • Swedish Medical Center-First Hill

    Seattle, Washington, 98122

  • Sidney Kimmel Cancer Center Washington Township

    Sewell, New Jersey, 08080

  • Ochsner LSU Health Saint Mary's Medical Center

    Shreveport, Louisiana, 71101

  • LSU Health Sciences Center at Shreveport

    Shreveport, Louisiana, 71103

  • Baptist Memorial Hospital and Cancer Center-Desoto

    Southhaven, Mississippi, 38671

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Spartanburg Medical Center - Mary Black Campus

    Spartanburg, South Carolina, 29307

  • Essentia Health Saint Mary's Hospital - Superior

    Superior, Wisconsin, 54880

  • Montefiore Medical Center-Einstein Campus

    The Bronx, New York, 10461

  • Montefiore Medical Center-Weiler Hospital

    The Bronx, New York, 10461

  • Sanford Thief River Falls Medical Center

    Thief River Falls, Minnesota, 56701

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Northwest Cancer Center - Valparaiso

    Valparaiso, Indiana, 46383

  • Essentia Health Virginia Clinic

    Virginia, Minnesota, 55792

  • Sentara Princess Anne Hospital

    Virginia Beach, Virginia, 23456

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • UW Cancer Center at ProHealth Care

    Waukesha, Wisconsin, 53188

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

  • Wexford Health and Wellness Pavilion

    Wexford, Pennsylvania, 15090

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

  • UMass Memorial Medical Center - University Campus

    Worcester, Massachusetts, 01655

Other trials in United States

Canada7 sites

  • Saint Joseph's Health Care London

    London, Ontario, N6A 4V2

  • Hopital Du Sacre-Coeur de Montreal

    Montreal, Quebec, H4J 1C5

  • Ottawa Hospital and Cancer Center-General Campus

    Ottawa, Ontario, K1H 8L6

  • CHU de Quebec-Hopital du Saint-Sacrement (HSS)

    Québec, Quebec, G1S 4L8

  • Odette Cancer Centre- Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • Mount Sinai Hospital

    Toronto, Ontario, M5G 1X5

  • BCCA-Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

Argentina1 site

  • CERIM

    Buenos Aires, 1425

Other trials in Argentina

Chile1 site

  • Hospital Sotero Del Rio

    Puente Alto, Santiago Metropolitan, 8207257

Other trials in Chile

Italy1 site

  • Ospedale Ca Foncello di Treviso - ULSS 2 Marca Trevigiana

    Treviso, 31100

Other trials in Italy

Peru1 site

  • Oncosalud S.A.C.

    Lima, Lima 41

Other trials in Peru

Puerto Rico1 site

  • San Juan City Hospital

    San Juan, 00936

Other trials in Puerto Rico

South Korea1 site

  • National Cancer Center-Korea

    Goyang-si, Gyeonggi-do, 410-769

Other trials in South Korea

Spain1 site

  • Parc Tauli Sabadell Hospital Universitari

    Sabadell, Barcelona, 08208

Other trials in Spain

Taiwan1 site

  • Taipei Veterans General Hospital

    Taipai, 112

Other trials in Taiwan

Thailand1 site

  • Chiang Mai University

    Chiang Mai, Muang, 50200

Other trials in Thailand

About this study

Official title: Tomosynthesis Mammographic Imaging Screening Trial (TMIST)

This randomized phase III trial studies digital tomosynthesis mammography and digital mammography in screening patients for breast cancer. Screening for breast cancer with tomosynthesis mammography may be superior to digital mammography for breast cancer screening and may help reduce the need for additional imaging or treatment.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

  1. 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.

Being tested
Digital Mammography, Digital Tomosynthesis Mammography, Laboratory Biomarker Analysis
Keywords
Digital Mammography, Breast Tomography, Screening Mammography, TMIST

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Digital MammographyProcedure or surgery

    Also called Full Field Digital Mammography, FFDM

    Undergo DM

  • Digital Tomosynthesis MammographyProcedure or surgery

    Also called DBT, Digital Breast Tomosynthesis, Digital Tomosynthesis of the Breast

    Undergo TM

  • Laboratory Biomarker AnalysisOther

    Also called Biomarker analysis, genetic analysis, PAM50

    Correlative studies

Study groups in NCT03233191
Study groupRoleWhat they receive
Arm A (digital mammography)ExperimentalPatients 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.
Receives: Procedure: Digital Mammography; Other: Laboratory Biomarker Analysis
Arm B (digital tomosynthesis mammography)ExperimentalPatients 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.
Receives: Procedure: Digital Tomosynthesis Mammography; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of women diagnosed with 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 follow up after the last screen

    The cumulative proportions of participants experiencing the primary endpoint in the two study arms will be compared. The primary comparison of the two study arms will be approached from an Intent-to-Treat perspective and will be based on a two-sided test for comparing binomial proportions.

    Measured: 4.5 years after last registration

Secondary outcomes (17)

  1. Agreement between local and expert study pathologists for all breast lesions (benign and malignant) biopsied during the five years of screening

    Measures of agreement such as kappa statistics and concordance coefficients to assess the agreement of local and central pathology readings. In addition, the variability among local pathologists will be examined with respect to the degree of agreement with the central study interpretation. This analysis will utilize mixed models with random effects for local pathologists. There will be up to two central study independent pathologist interpretations for each representative diagnostic slide set.

    Measured: Up to 8 years

  2. Breast Imaging-Reporting and Data System (BIRADS) imaging features

    The correlation between 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 will be examined. Using data on patients with cancer, estimates of the correlation between the two sets of features (BIRADS imaging features and histologic/genetic features) will be derived. Cluster analysis will be used to identify clusters of patients based on imaging features and will examine the association of these clusters with histology and genetic features. Using data from the fu

    Measured: Up to 8 years

  3. Breast-cancer-specific mortality

    Breast-cancer-specific mortality between the two study arms will be estimated and compared. Information on cancer recurrence and mortality will be obtained for a period of at least 4.5-8 years on all study participants. Mortality rates will be estimated as the ratio of the number of breast cancer deaths during a time period to the number of person-years at risk. Person-years will be measured as time from randomization to breast cancer death or censoring. Cumulative mortality rates from breast cancer at the end of the study period in each arm will be compared via the relative risk (rate ratio).

    Measured: Up to 8 years

  4. Centralized quality control (QC) monitoring program implementation

    Centralized QC monitoring program for both DM and TM, which provides rapid feedback on image quality, using quantitative tools, taking advantage of the automated analysis of digital images. The QC program will provide an auditable trail of QC activities and image quality parameters, while at the same time reducing QC effort required by the technologist at the site.

    Constant monitoring of data from all sites will occur, and Root Cause Analysis will be performed for non-compliant items. The remote monitoring system will be evaluated in terms of its percent ?up-time?, technologist compliance (vi

    Measured: Up to 8 years

  5. Diagnostic and predictive performance of tomosynthesis mammography (TM) and digital mammography (DM) [AUC]

    ROC analysis will be performed to compare the performance characteristics of DM vs TM at each screening visit

    Measured: Up to 8 years

  6. Assess the predictive performance of tomosynthesis mammography (TM) and digital mammography (DM)

    Compare the predictive characteristics (PPV,NPV,Sens, and Spec) of DM vs TM at each screening visit

    Measured: Up to 8 years

  7. Health care costs (including diagnostic procedures and cancer care received) as the result of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)

    Rates of utilization of key diagnostic procedures (e.g. extra TM or DM views, Ultrasound, Short-term interval follow-up, surgical consultation, percutaneous biopsy with, needle-localized open surgical biopsy, breast MRI) will be estimated; Medicare reimbursement costs will be used to derive a standardized measure of cost per participant; and these costs will be compared across the two study arms. These measures of cost will be compared across study arms using non-parametric methods.

    Measured: Up to 8 years

  8. Health care utilization (including cancer care received) of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)

    Rates of utilization of key diagnostic procedures (e.g. extra TM or DM views, Ultrasound, Short-term interval follow-up, surgical consultation, percutaneous biopsy with, needle-localized open surgical biopsy, breast MRI) will be estimated and compared across the two study arms. The comparisons will be made using regression modeling

    Measured: Up to 8 years

  9. Histologically malignant (true positive cases) and benign lesions (false positive cases)

    Classification of histologically benign-appearing lesions (false positive cases) will be explored as normal-like or tumor-like using the PAM50 gene expression assay subtype and low, medium, or high proliferation according to a PAM50 proliferation signature, and p53 mutant-like or wild-type-like according to a validated p53-dependent signature, and according to histological features. The benign-appearing (false positive) biopsies will be characterized using digital histologic analysis tools that capture percent of area represented by stroma, epithelium, and fat as well as the density of nuclei

    Measured: Up to 8 years

  10. Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms

    Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms will be estimated and compared, overall and stratified on whether cancers were detected through screening or as interval cancers. subtypes in each arm and to compare them across arms. The analysis will be performed overall, and stratified by screen detected or interval detected. Estimates of the prevalence of subtypes and confidence intervals will be developed for each screening round and for the full period of screening. The comparison of rates across arms will be based on multinom

    Measured: Up to 8 years

  11. Proportion of women diagnosed with an ?advanced? breast cancer in the two arms

    The potential effect of age, menopausal and hormonal status, breast density, and family cancer history will be assessed on the primary endpoint difference between the two arms. Regression modeling will be used to assess the effect of age, menopausal and hormonal status, breast density, and family cancer history. Multiple imputation will be used to handle missing data in the response and the covariates, and a sensitivity analysis to assumptions about the missing data will be performed. An exploratory analysis using alternative definitions of the primary endpoint will also be conducted in order

    Measured: Up to 8 years

  12. Quality control (QC) tests useful for determination of image quality and those that are predictive of device failure

    QC tests that are useful for determination of image quality and those that are predictive of device failure will be evaluated, in order to recommend an optimal QC program for TM. Tests that are most sensitive to changes in system performance will be established and tests that are inferior and/or redundant and can be eliminated. Changes will be tracked against site records of alterations or repairs to the system, recalibration and changes in imaging parameters. Changes in test results will be observed and if they are suggestive that remedial action is required, we will determine after such acti

    Measured: Up to 8 years

  13. Rate of interval cancers

    The rate of interval cancers for TM and DM will be compared and the mechanism of diagnosis for these interval cancers will be assessed with categorization by symptomatic vs asymptomatic, and how detected: diagnosed via physical examination, mammography, ultrasound (US), magnetic resonance imaging (MRI) or other technologies. Interval cancers are those that occur between screening examinations. Interval cancer rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. The di

    Measured: Up to 8 years

  14. Recall rates

    The recall rates for TM versus (vs) DM will be compared. Recall rates are defined as the number of screening examinations that are interpreted as BIRADS 0, 3, 4 and 5 divided by the total number of screening examinations. Recall rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. Logistic regression will be used to analyze potential differences across patient subsets.

    Measured: Up to 8 years

  15. Biopsy rates

    The biopsy rates for TM versus (vs) DM will be compared. biopsy rates are defined as the number of biopsies divided by the total number of screening examinations. rates for each screening occasion and over the full set of screens will be estimated using Wilson intervals and compared across arms using two-sided tests for binomial proportions. Logistic regression will be used to analyze potential differences across patient subsets

    Measured: Up to 8 years

  16. Task-based measure of image quality

    Task-based measures of image quality will be refined and implemented to assess the effects of technical parameters, including machine type, and detector spatial and contrast resolution on diagnostic accuracy for TM. the diagnostic accuracy of the resulting Task-based analysis, using mathematical observers, will be assessed from image information using techniques based on signal and noise transfer.

    Measured: Up to 8 years

  17. Variability of quality control parameters

    The variability of standard quality control parameters will be assessed and compared temporally, within, and across sites for both DM and TM.

    Measured: Up to 8 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2017
  2. Study start28 Sep 2017
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Screening
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomized to either Digital Breast Tomography (TM) or Full Field Digital Mammography (DM)
Masking
None (open label)
Enrolment
108,508 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03233191
Sponsor's protocol ID
EA1151
Other IDs
NCI-2017-01111, EA1151, EA1151, EA1151, U10CA180820, U10CA180794
Status last verified
Oct 2026
First submitted
5 Jul 2017
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Lee JM, Ichikawa L, Su YR, Noguchi N, Hubbard RA, Kerlikowske K, Specht JM, O'Meara ES, Henderson LM, Houssami N. Comparative Accuracy of Digital Breast Tomosynthesis and Digital Mammography for Surveillance After Breast Cancer Treatment. J Natl Compr Canc Netw. 2025 Oct 16;23(11):445-452. doi: 10.6004/jnccn.2025.7057.

    PubMed 41101341

  • 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.

    PubMed 37830895

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Digital Mammography, Digital Tomosynthesis Mammography and Laboratory Biomarker Analysis in people with Breast Screening, run by ECOG-ACRIN Cancer Research Group at 149 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 149 sites in United States, Canada, Argentina, Chile, Italy and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of women diagnosed with 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 follow up after the last screen (time frame: 4.5 years after last registration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03233191, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.

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