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

April 29, 2026 updated by: ECOG-ACRIN Cancer Research Group

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
108508

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, 1425
        • CERIM
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BCCA-Vancouver Cancer Centre
    • Ontario
      • London, Ontario, Canada, N6A 4V2
        • Saint Joseph's Health Care London
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital and Cancer Center-General Campus
      • Toronto, Ontario, Canada, M5G 1X5
        • Mount Sinai Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Odette Cancer Centre- Sunnybrook Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • Hopital Du Sacre-Coeur de Montreal
      • Québec, Quebec, Canada, G1S 4L8
        • CHU de Quebec-Hopital du Saint-Sacrement (HSS)
  • Chile
    • Santiago Metropolitan
      • Puente Alto, Santiago Metropolitan, Chile, 8207257
        • Hospital Sotero Del Rio
  • Italy
      • Treviso, Italy, 31100
        • Ospedale Ca Foncello di Treviso - ULSS 2 Marca Trevigiana
  • Peru
      • Lima, Peru, Lima 41
        • Oncosalud S.A.C.
  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • San Juan City Hospital
  • South Korea
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, South Korea, 410-769
        • National Cancer Center-Korea
  • Spain
    • Barcelona
      • Sabadell, Barcelona, Spain, 08208
        • Parc Tauli Sabadell Hospital Universitari
  • Taiwan
      • Taipai, Taiwan, 112
        • Taipei Veterans General Hospital
  • Thailand
    • Muang
      • Chiang Mai, Muang, Thailand, 50200
        • Chiang Mai University
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham Cancer Center
      • Mobile, Alabama, United States, 36607
        • Mobile Infirmary Medical Center
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic Hospital in Arizona
      • Phoenix, Arizona, United States, 85006
        • Banner-University Medical Center Phoenix
      • Phoenix, Arizona, United States, 85006
        • University of Arizona College of Medicine Phoenix
      • Phoenix, Arizona, United States, 85008
        • Valleywise Comprehensive Health Center - Phoenix
      • Scottsdale, Arizona, United States, 85258
        • Scottsdale Medical Imaging Limited
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences
    • California
      • Bakersfield, California, United States, 93306
        • Kern Radiology Medical Group Inc
      • Los Angeles, California, United States, 90033
        • USC / Norris Comprehensive Cancer Center
      • Los Angeles, California, United States, 90033
        • Los Angeles General Medical Center
      • Modesto, California, United States, 95356
        • Kaiser Permanente-Modesto
      • San Francisco, California, United States, 94110
        • Zuckerberg San Francisco General Hospital
    • Colorado
      • Aurora, Colorado, United States, 80045
        • UCHealth University of Colorado Hospital
      • Colorado Springs, Colorado, United States, 80907
        • Penrose-Saint Francis Healthcare
      • Denver, Colorado, United States, 80209
        • The Women's Imaging Center
      • Englewood, Colorado, United States, 80112
        • Radiology Imaging Associates
      • Highlands Ranch, Colorado, United States, 80129
        • UCHealth Highlands Ranch Hospital
      • Lone Tree, Colorado, United States, 80124
        • UCHealth Lone Tree Health Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • Helen F Graham Cancer Center
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • MedStar Georgetown University Hospital
    • Florida
      • Jacksonville, Florida, United States, 32209
        • University of Florida Health Science Center - Jacksonville
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
      • Braselton, Georgia, United States, 30517
        • Northeast Georgia Medical Center Braselton
      • Savannah, Georgia, United States, 31405
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queen's Medical Center
    • Idaho
      • Boise, Idaho, United States, 83706
        • Saint Alphonsus Cancer Care Center-Boise
      • Boise, Idaho, United States, 83712
        • Saint Luke's Cancer Institute - Boise
    • Illinois
      • Bloomington, Illinois, United States, 61701
        • Bromenn Lifecare Center
      • Chicago, Illinois, United States, 60612
        • John H Stroger Jr Hospital of Cook County
      • Danville, Illinois, United States, 61832
        • Carle at The Riverfront
      • Danville, Illinois, United States, 61832
        • Carle on Fairchild
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital
      • Hoopeston, Illinois, United States, 60942
        • Carle Hoopeston Regional Health Center
      • Mattoon, Illinois, United States, 61938
        • Carle Physician Group-Mattoon/Charleston
      • Normal, Illinois, United States, 61761
        • Bromenn Regional Medical Center
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Indiana
      • Hobart, Indiana, United States, 46342
        • Saint Mary Medical Center
      • Indianapolis, Indiana, United States, 46202
        • Indiana University/Melvin and Bren Simon Cancer Center
      • Munster, Indiana, United States, 46321
        • The Community Hospital
      • Munster, Indiana, United States, 46321
        • Women's Diagnostic Center - Munster
      • Valparaiso, Indiana, United States, 46383
        • Northwest Cancer Center - Valparaiso
    • Iowa
      • Des Moines, Iowa, United States, 50314
        • Mercy Medical Center - Des Moines
      • Iowa City, Iowa, United States, 52242
        • University of Iowa/Holden Comprehensive Cancer Center
    • Kentucky
      • Owensboro, Kentucky, United States, 42303
        • Owensboro Health Mitchell Memorial Cancer Center
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Mary Bird Perkins Cancer Center
      • Baton Rouge, Louisiana, United States, 70817
        • Woman's Hospital
      • New Orleans, Louisiana, United States, 70112
        • Tulane University School of Medicine
      • New Orleans, Louisiana, United States, 70112
        • University Medical Center New Orleans
      • Shreveport, Louisiana, United States, 71103
        • LSU Health Sciences Center at Shreveport
      • Shreveport, Louisiana, United States, 71101
        • Ochsner LSU Health Saint Mary's Medical Center
    • Maryland
      • Kensington, Maryland, United States, 20895
        • Kaiser Permanente - Kensington Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Worcester, Massachusetts, United States, 01655
        • UMass Memorial Medical Center - University Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
      • Ann Arbor, Michigan, United States, 48106
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
      • Battle Creek, Michigan, United States, 49017
        • Bronson Battle Creek
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Wayne State University/Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Weisberg Cancer Treatment Center
      • Grand Rapids, Michigan, United States, 49503
        • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
      • Kalamazoo, Michigan, United States, 49007
        • West Michigan Cancer Center
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Essentia Health Cancer Center
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Medical Center
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Clinic - Saint Louis Park
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital
      • Thief River Falls, Minnesota, United States, 56701
        • Sanford Thief River Falls Medical Center
      • Virginia, Minnesota, United States, 55792
        • Essentia Health Virginia Clinic
    • Mississippi
      • Southhaven, Mississippi, United States, 38671
        • Baptist Memorial Hospital and Cancer Center-Desoto
    • Nevada
      • Carson City, Nevada, United States, 89703
        • Carson Tahoe Regional Medical Center
    • New Jersey
      • Flemington, New Jersey, United States, 08822
        • Hunterdon Medical Center
      • New Brunswick, New Jersey, United States, 08901
        • Saint Peter's University Hospital
      • Red Bank, New Jersey, United States, 07701
        • Riverview Medical Center/Booker Cancer Center
      • Sewell, New Jersey, United States, 08080
        • Sidney Kimmel Cancer Center Washington Township
    • New Mexico
      • Albuquerque, New Mexico, United States, 87106
        • University of New Mexico Cancer Center
    • New York
      • Elmira, New York, United States, 14905
        • Arnot Ogden Medical Center/Falck Cancer Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10032
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
      • New York, New York, United States, 10065
        • NYP/Weill Cornell Medical Center
      • Rochester, New York, United States, 14642
        • University of Rochester
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Einstein Campus
      • The Bronx, New York, United States, 10461
        • Montefiore Medical Center-Weiler Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • UNC Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
      • Hillsborough, North Carolina, United States, 27278
        • University of North Carolina-Hillsborough Campus
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest University Health Sciences
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
        • Sanford Bismarck Medical Center
      • Fargo, North Dakota, United States, 58103
        • Southpointe-Sanford Medical Center Fargo
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Cleveland Clinic Cancer Center Beachwood
      • Canton, Ohio, United States, 44710
        • Aultman Health Foundation
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati Cancer Center-UC Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
    • Pennsylvania
      • Easton, Pennsylvania, United States, 18042
        • Easton Hospital
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Milton S Hershey Medical Center
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Pennsylvania Hospital
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Wexford, Pennsylvania, United States, 15090
        • Wexford Health and Wellness Pavilion
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Greenville Memorial Hospital
      • Mt. Pleasant, South Carolina, United States, 29464
        • MUSC Health East Cooper
      • Spartanburg, South Carolina, United States, 29303
        • Spartanburg Medical Center
      • Spartanburg, South Carolina, United States, 29307
        • Spartanburg Medical Center - Mary Black Campus
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee - Knoxville
      • Memphis, Tennessee, United States, 38120
        • Baptist Memorial Hospital and Cancer Center-Memphis
      • Memphis, Tennessee, United States, 38120
        • Baptist Memorial Hospital for Women
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University/Ingram Cancer Center
      • Nashville, Tennessee, United States, 37204
        • Vanderbilt Breast Center at One Hundred Oaks
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern/Simmons Cancer Center-Dallas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center
      • Houston, Texas, United States, 77030
        • Memorial Hermann Texas Medical Center
      • Houston, Texas, United States, 77098
        • Memorial Hermann Imaging Center - Upper Kirby
      • San Antonio, Texas, United States, 78229
        • University Hospital
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • University of Virginia Cancer Center
      • Midlothian, Virginia, United States, 23113
        • Bon Secours Westchester Emergency Center
      • Norfolk, Virginia, United States, 23507
        • Sentara Norfolk General Hospital
      • Norfolk, Virginia, United States, 23502
        • Sentara Leigh Hospital
      • Virginia Beach, Virginia, United States, 23456
        • Sentara Princess Anne Hospital
    • Washington
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center-First Hill
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • West Virginia University Healthcare
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • ThedaCare Regional Cancer Center
      • La Crosse, Wisconsin, United States, 54601
        • Gundersen Lutheran Medical Center
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Carbone Cancer Center - University Hospital
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Medical Center-Marshfield
      • Mukwonago, Wisconsin, United States, 53149
        • ProHealth D N Greenwald Center
      • Oconomowoc, Wisconsin, United States, 53066
        • ProHealth Oconomowoc Memorial Hospital
      • Superior, Wisconsin, United States, 54880
        • Essentia Health Saint Mary's Hospital - Superior
      • Waukesha, Wisconsin, United States, 53188
        • UW Cancer Center at ProHealth Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other Names:
  • genetic analysis
  • Biomarker analysis
  • PAM50
Procedure: Digital Mammography
Undergo DM
Other Names:
  • Full Field Digital Mammography
  • FFDM
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies
Other Names:
  • genetic analysis
  • Biomarker analysis
  • PAM50
Procedure: Digital Tomosynthesis Mammography
Undergo TM
Other Names:
  • DBT
  • Digital Breast Tomosynthesis
  • Digital Tomosynthesis of the Breast

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
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.
4.5 years after last registration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Agreement between local and expert study pathologists for all breast lesions (benign and malignant) biopsied during the five years of screening
Time Frame: Up to 8 years
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.
Up to 8 years
Breast Imaging-Reporting and Data System (BIRADS) imaging features
Time Frame: Up to 8 years
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
Up to 8 years
Breast-cancer-specific mortality
Time Frame: Up to 8 years
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).
Up to 8 years
Centralized quality control (QC) monitoring program implementation
Time Frame: Up to 8 years

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
Up to 8 years
Diagnostic and predictive performance of tomosynthesis mammography (TM) and digital mammography (DM) [AUC]
Time Frame: Up to 8 years
ROC analysis will be performed to compare the performance characteristics of DM vs TM at each screening visit
Up to 8 years
Assess the predictive performance of tomosynthesis mammography (TM) and digital mammography (DM)
Time Frame: Up to 8 years
Compare the predictive characteristics (PPV,NPV,Sens, and Spec) of DM vs TM at each screening visit
Up to 8 years
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)
Time Frame: Up to 8 years
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.
Up to 8 years
Health care utilization (including cancer care received) of an episode of breast cancer screening by tomosynthesis mammography (TM) versus digital mammography (DM)
Time Frame: Up to 8 years
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
Up to 8 years
Histologically malignant (true positive cases) and benign lesions (false positive cases)
Time Frame: Up to 8 years
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
Up to 8 years
Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) and p53 signature in the two arms
Time Frame: Up to 8 years
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
Up to 8 years
Proportion of women diagnosed with an ?advanced? breast cancer in the two arms
Time Frame: Up to 8 years
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
Up to 8 years
Quality control (QC) tests useful for determination of image quality and those that are predictive of device failure
Time Frame: Up to 8 years
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
Up to 8 years
Rate of interval cancers
Time Frame: Up to 8 years
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
Up to 8 years
Recall rates
Time Frame: Up to 8 years
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.
Up to 8 years
Biopsy rates
Time Frame: Up to 8 years
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
Up to 8 years
Task-based measure of image quality
Time Frame: Up to 8 years
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.
Up to 8 years
Variability of quality control parameters
Time Frame: Up to 8 years
The variability of standard quality control parameters will be assessed and compared temporally, within, and across sites for both DM and TM.
Up to 8 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
ECOG-ACRIN Cancer Research Group

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)
Canadian Cancer Trials Group (CCTG)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Etta Pisano, ECOG-ACRIN Cancer Research Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 28, 2017

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 5, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • EA1151 (Other Identifier: CTEP)
  • U10CA180820 (U.S. NIH Grant/Contract)
  • NCI-2017-01111 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180794 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Conditions

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