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

June 21, 2023 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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

128905

Phase

  • 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
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • Recruiting
        • BCCA-Vancouver Cancer Centre
        • Principal Investigator:
          • Paula B. Gordon
        • Contact:
          • Site Public Contact
          • Phone Number: 888-939-3333
    • Ontario
      • London, Ontario, Canada, N6A 4V2
        • Recruiting
        • Saint Joseph's Health Centre
        • Principal Investigator:
          • Anat Kornecki
        • Contact:
      • Ottawa, Ontario, Canada, K1H 8L6
        • Recruiting
        • Ottawa Hospital and Cancer Center-General Campus
        • Contact:
          • Site Public Contact
          • Phone Number: 613-761-4395
        • Principal Investigator:
          • Jean M. Seely
      • Toronto, Ontario, Canada, M4N 3M5
        • Recruiting
        • Odette Cancer Centre- Sunnybrook Health Sciences Centre
        • Principal Investigator:
          • Roberta A. Jong
        • Contact:
          • Site Public Contact
          • Phone Number: 416-480-5000
      • Toronto, Ontario, Canada, M5G 1X5
        • Recruiting
        • Mount Sinai Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 416-586-4800
        • Principal Investigator:
          • Vivianne A. Freitas
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • Recruiting
        • Hôpital du Sacré-Coeur de Montreal
        • Contact:
          • Site Public Contact
          • Phone Number: 514-338-2172
        • Principal Investigator:
          • Caroline Samson
      • Quebec City, Quebec, Canada, G1S 4L8
        • Recruiting
        • CHU de Quebec-Hopital du Saint-Sacrement (HSS)
        • Contact:
        • Principal Investigator:
          • Christine Desbiens
  • Korea, Republic of
    • Gyeonggi-do
      • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
        • Recruiting
        • National Cancer Center-Korea
        • Principal Investigator:
          • Chan Wha Lee
        • Contact:
          • Site Public Contact
          • Phone Number: 82-31-920-1934
  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • Recruiting
        • San Juan City Hospital
        • Principal Investigator:
          • Luis Baez-Diaz
        • Contact:
          • Site Public Contact
          • Phone Number: 787-763-1296
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham Cancer Center
        • Principal Investigator:
          • Stefanie A. Woodard
        • Contact:
      • Mobile, Alabama, United States, 36607
        • Recruiting
        • Mobile Infirmary Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 251-435-3942
        • Principal Investigator:
          • Travis Harris
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • Recruiting
        • Banner-University Medical Center Phoenix
        • Principal Investigator:
          • Michael F. Morris
        • Contact:
      • Phoenix, Arizona, United States, 85054
        • Recruiting
        • Mayo Clinic Hospital in Arizona
        • Principal Investigator:
          • Katie N. Hunt
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
      • Phoenix, Arizona, United States, 85006
        • Suspended
        • University of Arizona College of Medicine Phoenix
      • Phoenix, Arizona, United States, 85008
        • Recruiting
        • Valleywise Comprehensive Health Center - Phoenix
        • Contact:
          • Site Public Contact
          • Phone Number: 602-344-5775
        • Principal Investigator:
          • Christina Ferraro
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • Scottsdale Medical Imaging Limited
        • Contact:
        • Principal Investigator:
          • Sarah Palestrant
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Recruiting
        • University of Arkansas for Medical Sciences
        • Principal Investigator:
          • Gwendolyn M. Bryant-Smith
        • Contact:
          • Site Public Contact
          • Phone Number: 501-686-8274
    • California
      • Bakersfield, California, United States, 93306
        • Suspended
        • Kern Radiology Medical Group Inc
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC / Norris Comprehensive Cancer Center
        • Principal Investigator:
          • Linda H. Larsen
        • Contact:
          • Site Public Contact
          • Phone Number: 323-865-0451
      • Los Angeles, California, United States, 90033
        • Recruiting
        • Los Angeles County-USC Medical Center
        • Principal Investigator:
          • Linda H. Larsen
        • Contact:
          • Site Public Contact
          • Phone Number: 323-865-0451
      • San Francisco, California, United States, 94110
        • Recruiting
        • Zuckerberg San Francisco General Hospital
        • Principal Investigator:
          • Rita I. Freimanis
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital
        • Principal Investigator:
          • Dulcy E. Wolverton
        • Contact:
          • Site Public Contact
          • Phone Number: 720-848-0650
      • Colorado Springs, Colorado, United States, 80907
        • Recruiting
        • Penrose-Saint Francis Healthcare
        • Contact:
        • Principal Investigator:
          • Richard L. Deming
      • Denver, Colorado, United States, 80209
        • Recruiting
        • The Women's Imaging Center
        • Principal Investigator:
          • Nicholas DiBella
        • Contact:
      • Englewood, Colorado, United States, 80112
        • Suspended
        • Radiology Imaging Associates
      • Highlands Ranch, Colorado, United States, 80129
        • Recruiting
        • UCHealth Highlands Ranch Hospital
        • Principal Investigator:
          • Dulcy E. Wolverton
        • Contact:
          • Site Public Contact
          • Phone Number: 720-848-0650
      • Lone Tree, Colorado, United States, 80124
        • Active, not recruiting
        • UCHealth Lone Tree Health Center
    • Delaware
      • Newark, Delaware, United States, 19713
        • Recruiting
        • Helen F Graham Cancer Center
        • Principal Investigator:
          • Gregory A. Masters
        • Contact:
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • MedStar Georgetown University Hospital
        • Principal Investigator:
          • Judy H. Song
        • Contact:
          • Site Public Contact
          • Phone Number: 202-444-2223
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Recruiting
        • University of Florida Health Science Center - Jacksonville
        • Contact:
          • Site Public Contact
          • Phone Number: 888-254-7581
        • Principal Investigator:
          • Parlyn D. Hatch
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Northside Hospital
        • Principal Investigator:
          • Lynn D. Baxter
        • Contact:
      • Braselton, Georgia, United States, 30517
        • Recruiting
        • Northeast Georgia Medical Center Braselton
        • Contact:
        • Principal Investigator:
          • Charles H. Nash
      • Savannah, Georgia, United States, 31405
        • Recruiting
        • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
        • Contact:
        • Principal Investigator:
          • Howard A. Zaren
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Recruiting
        • Queen's Medical Center
        • Principal Investigator:
          • Erin Capps
        • Contact:
          • Site Public Contact
          • Phone Number: 808-545-8548
    • Idaho
      • Boise, Idaho, United States, 83712
        • Recruiting
        • Saint Luke's Cancer Institute - Boise
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
      • Boise, Idaho, United States, 83706
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Boise
        • Contact:
        • Principal Investigator:
          • John M. Schallenkamp
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • John H Stroger Jr Hospital of Cook County
        • Contact:
          • Site Public Contact
          • Phone Number: 312-864-5204
        • Principal Investigator:
          • Thomas E. Lad
      • Danville, Illinois, United States, 61832
        • Recruiting
        • Carle on Fairchild
        • Contact:
        • Principal Investigator:
          • Kendrith M. Rowland
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Hoopeston, Illinois, United States, 60942
        • Recruiting
        • Carle Hoopeston Regional Health Center
        • Contact:
        • Principal Investigator:
          • Kendrith M. Rowland
      • Mattoon, Illinois, United States, 61938
        • Recruiting
        • Carle Physician Group-Mattoon/Charleston
        • Contact:
        • Principal Investigator:
          • Kendrith M. Rowland
      • Urbana, Illinois, United States, 61801
        • Recruiting
        • Carle Cancer Center
        • Contact:
        • Principal Investigator:
          • Kendrith M. Rowland
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Recruiting
        • Indiana University/Melvin and Bren Simon Cancer Center
        • Principal Investigator:
          • Steven M. Westphal
        • Contact:
      • Munster, Indiana, United States, 46321
        • Recruiting
        • The Community Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 219-836-3349
        • Principal Investigator:
          • Mohamad Kassar
      • Munster, Indiana, United States, 46321
        • Recruiting
        • Women's Diagnostic Center - Munster
        • Contact:
        • Principal Investigator:
          • Kendrith M. Rowland
    • Iowa
      • Des Moines, Iowa, United States, 50314
        • Recruiting
        • Mercy Medical Center - Des Moines
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa/Holden Comprehensive Cancer Center
        • Principal Investigator:
          • Fabiana Policeni
        • Contact:
          • Site Public Contact
          • Phone Number: 800-237-1225
    • Kentucky
      • Owensboro, Kentucky, United States, 42303
        • Recruiting
        • Owensboro Health Mitchell Memorial Cancer Center
        • Principal Investigator:
          • Patrick G. Padgett
        • Contact:
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70809
        • Active, not recruiting
        • Mary Bird Perkins Cancer Center
      • Baton Rouge, Louisiana, United States, 70817
        • Recruiting
        • Woman's Hospital
        • Contact:
        • Principal Investigator:
          • James F. Ruiz
      • New Orleans, Louisiana, United States, 70112
        • Recruiting
        • University Medical Center New Orleans
        • Principal Investigator:
          • Mignonne B. Morrell
        • Contact:
      • New Orleans, Louisiana, United States, 70112
        • Recruiting
        • Tulane University Health Sciences Center
        • Principal Investigator:
          • Kendra M. Harris
        • Contact:
          • Site Public Contact
          • Phone Number: 504-988-6121
      • Shreveport, Louisiana, United States, 71103
        • Recruiting
        • LSU Health Sciences Center at Shreveport
        • Principal Investigator:
          • Jerry McLarty
        • Contact:
      • Shreveport, Louisiana, United States, 71101
        • Recruiting
        • Ochsner LSU Health Saint Mary's Medical Center
        • Principal Investigator:
          • Jerry McLarty
        • Contact:
    • Maryland
      • Kensington, Maryland, United States, 20895
        • Recruiting
        • Kaiser Permanente - Kensington Medical Center
        • Principal Investigator:
          • Ainsley V. MacLean
        • Contact:
          • Site Public Contact
          • Phone Number: 301-816-7218
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Recruiting
        • Boston Medical Center
        • Principal Investigator:
          • Michael D. Fishman
        • Contact:
          • Site Public Contact
          • Phone Number: 617-638-8265
      • Worcester, Massachusetts, United States, 01655
        • Recruiting
        • UMass Memorial Medical Center - University Campus
        • Principal Investigator:
          • Gopal Vijayaraghavan
        • Contact:
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Recruiting
        • Saint Joseph Mercy Hospital
        • Contact:
        • Principal Investigator:
          • Philip J. Stella
      • Ann Arbor, Michigan, United States, 48109
        • Recruiting
        • University of Michigan Comprehensive Cancer Center
        • Principal Investigator:
          • Stephanie Patterson
        • Contact:
          • Site Public Contact
          • Phone Number: 800-865-1125
      • Battle Creek, Michigan, United States, 49017
        • Recruiting
        • Bronson Battle Creek
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Detroit, Michigan, United States, 48201
        • Recruiting
        • Wayne State University/Karmanos Cancer Institute
        • Principal Investigator:
          • Alit J. Yousif
        • Contact:
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Contact:
        • Principal Investigator:
          • Ding Wang
      • Farmington Hills, Michigan, United States, 48334
        • Recruiting
        • Weisberg Cancer Treatment Center
        • Principal Investigator:
          • Alit J. Yousif
        • Contact:
      • Grand Rapids, Michigan, United States, 49503
        • Recruiting
        • Spectrum Health at Butterworth Campus
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • Kalamazoo, Michigan, United States, 49007
        • Recruiting
        • West Michigan Cancer Center
        • Contact:
        • Principal Investigator:
          • Kathleen J. Yost
      • West Bloomfield, Michigan, United States, 48322
        • Recruiting
        • Henry Ford West Bloomfield Hospital
        • Contact:
        • Principal Investigator:
          • Ding Wang
    • Minnesota
      • Duluth, Minnesota, United States, 55805
        • Recruiting
        • Essentia Health Cancer Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Minneapolis, Minnesota, United States, 55415
        • Recruiting
        • Hennepin County Medical Center
        • Contact:
        • Principal Investigator:
          • David M. King
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Principal Investigator:
          • Katie N. Hunt
        • Contact:
          • Site Public Contact
          • Phone Number: 855-776-0015
      • Saint Louis Park, Minnesota, United States, 55416
        • Recruiting
        • Park Nicollet Clinic - Saint Louis Park
        • Contact:
        • Principal Investigator:
          • David M. King
      • Saint Paul, Minnesota, United States, 55101
        • Recruiting
        • Regions Hospital
        • Contact:
        • Principal Investigator:
          • David M. King
      • Thief River Falls, Minnesota, United States, 56701
        • Recruiting
        • Sanford Thief River Falls Medical Center
        • Principal Investigator:
          • Preston D. Steen
        • Contact:
          • Site Public Contact
          • Phone Number: 605-312-3320
      • Virginia, Minnesota, United States, 55792
        • Recruiting
        • Essentia Health Virginia Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
    • Nevada
      • Carson City, Nevada, United States, 89703
        • Recruiting
        • Carson Tahoe Regional Medical Center
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
    • New Jersey
      • Flemington, New Jersey, United States, 08822
        • Recruiting
        • Hunterdon Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 908-237-2330
        • Principal Investigator:
          • Kenneth B. Blankstein
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Saint Peter's University Hospital
        • Principal Investigator:
          • Susan A. McManus
        • Contact:
      • Red Bank, New Jersey, United States, 07701
        • Recruiting
        • Riverview Medical Center/Booker Cancer Center
        • Principal Investigator:
          • Bokran Won
        • Contact:
          • Site Public Contact
          • Phone Number: 732-530-2382
      • Sewell, New Jersey, United States, 08080
        • Recruiting
        • Sidney Kimmel Cancer Center Washington Township
        • Principal Investigator:
          • Jason Shames
        • Contact:
    • New Mexico
      • Albuquerque, New Mexico, United States, 87102
        • Recruiting
        • University of New Mexico Cancer Center
        • Principal Investigator:
          • Ursa A. Brown-Glaberman
        • Contact:
    • New York
      • Bronx, New York, United States, 10461
        • Recruiting
        • Montefiore Medical Center-Einstein Campus
        • Principal Investigator:
          • Della F. Makower
        • Contact:
      • Bronx, New York, United States, 10461
        • Suspended
        • Montefiore Medical Center-Weiler Hospital
      • Elmira, New York, United States, 14905
        • Recruiting
        • Arnot Ogden Medical Center/Falck Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 607-271-7000
        • Principal Investigator:
          • Chi K. Tsang
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Principal Investigator:
          • Allison Borowski
        • Contact:
      • New York, New York, United States, 10065
        • Recruiting
        • NYP/Weill Cornell Medical Center
        • Principal Investigator:
          • Michele B. Drotman
        • Contact:
          • Site Public Contact
          • Phone Number: 212-746-1848
      • New York, New York, United States, 10065
        • Active, not recruiting
        • Memorial Sloan Kettering Cancer Center
      • Rochester, New York, United States, 14642
        • Recruiting
        • University of Rochester
        • Contact:
          • Site Public Contact
          • Phone Number: 585-275-5830
        • Principal Investigator:
          • Paul M. Barr
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • UNC Lineberger Comprehensive Cancer Center
        • Principal Investigator:
          • Cherie Kuzmiak
        • Contact:
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Lars J. Grimm
        • Contact:
          • Site Public Contact
          • Phone Number: 888-275-3853
      • Hillsborough, North Carolina, United States, 27278
        • Recruiting
        • University of North Carolina-Hillsborough Campus
        • Principal Investigator:
          • Cherie Kuzmiak
        • Contact:
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Principal Investigator:
          • Kelly Brozzetti Cronin
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
    • North Dakota
      • Bismarck, North Dakota, United States, 58501
      • Fargo, North Dakota, United States, 58103
        • Recruiting
        • Southpointe-Sanford Medical Center Fargo
        • Principal Investigator:
          • Preston D. Steen
        • Contact:
          • Site Public Contact
          • Phone Number: 605-312-3320
    • Ohio
      • Canton, Ohio, United States, 44710
        • Recruiting
        • Aultman Health Foundation
        • Contact:
        • Principal Investigator:
          • Shruti Trehan
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Cancer Center-UC Medical Center
        • Principal Investigator:
          • Lawrence D. Sobel
        • Contact:
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Foundation
        • Principal Investigator:
          • Alice Rim
        • Contact:
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Principal Investigator:
          • Jeffrey R. Hawley
        • Contact:
    • Pennsylvania
      • Easton, Pennsylvania, United States, 18042
        • Suspended
        • Easton Hospital
      • Hershey, Pennsylvania, United States, 17033-0850
        • Recruiting
        • Penn State Milton S Hershey Medical Center
        • Principal Investigator:
          • Rebecca T. Sivarajah
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Principal Investigator:
          • Jason Shames
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Pennsylvania Hospital
        • Principal Investigator:
          • Brian S. Englander
        • Contact:
          • Site Public Contact
          • Phone Number: 800-789-7366
      • Philadelphia, Pennsylvania, United States, 19111
        • Recruiting
        • Fox Chase Cancer Center
        • Principal Investigator:
          • Meghan Boros
        • Contact:
          • Site Public Contact
          • Phone Number: 215-728-4790
      • Pittsburgh, Pennsylvania, United States, 15212
        • Recruiting
        • Allegheny General Hospital
        • Principal Investigator:
          • Zidnia M. Conde-Colon
        • Contact:
          • Site Public Contact
          • Phone Number: 877-284-2000
      • Wexford, Pennsylvania, United States, 15090
        • Recruiting
        • Wexford Health and Wellness Pavilion
        • Principal Investigator:
          • Zidnia M. Conde-Colon
        • Contact:
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina
        • Principal Investigator:
          • Dag Pavic
        • Contact:
      • Columbia, South Carolina, United States, 29203
        • Recruiting
        • Prisma Health Richland Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Ki Y. Chung
      • Greenville, South Carolina, United States, 29605
        • Recruiting
        • Prisma Health Greenville Memorial Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 864-241-6251
        • Principal Investigator:
          • Ki Y. Chung
      • Mount Pleasant, South Carolina, United States, 29464
        • Recruiting
        • MUSC Health East Cooper
        • Principal Investigator:
          • Dag Pavic
        • Contact:
      • Spartanburg, South Carolina, United States, 29303
        • Recruiting
        • Spartanburg Medical Center
        • Contact:
        • Principal Investigator:
          • Amarinthia (Amy) Curtis
      • Spartanburg, South Carolina, United States, 29307
        • Recruiting
        • Spartanburg Medical Center - Mary Black Campus
        • Principal Investigator:
          • Amarinthia (Amy) Curtis
        • Contact:
          • Site Public Contact
          • Phone Number: 864-560-6812
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • University of Tennessee - Knoxville
        • Principal Investigator:
          • Garnetta I. Morin-Ducote
        • Contact:
          • Site Public Contact
          • Phone Number: 865-544-9773
      • Memphis, Tennessee, United States, 38120
        • Recruiting
        • Baptist Memorial Hospital for Women
        • Principal Investigator:
          • Evelyn W. Gayden
        • Contact:
      • Memphis, Tennessee, United States, 38120
        • Suspended
        • Baptist Memorial Hospital and Cancer Center-Memphis
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University/Ingram Cancer Center
        • Principal Investigator:
          • Reagan Leverett
        • Contact:
          • Site Public Contact
          • Phone Number: 800-811-8480
      • Nashville, Tennessee, United States, 37204
        • Recruiting
        • Vanderbilt Breast Center at One Hundred Oaks
        • Principal Investigator:
          • Reagan Leverett
        • Contact:
          • Site Public Contact
          • Phone Number: 800-811-8480
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Principal Investigator:
          • W. P. Evans
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Principal Investigator:
          • Gary J. Whitman
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • Memorial Hermann Texas Medical Center
        • Principal Investigator:
          • Claudia Cotes
        • Contact:
          • Site Public Contact
          • Phone Number: 713-792-3245
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • University Hospital
        • Contact:
        • Principal Investigator:
          • Pamela M. Otto
    • Virginia
      • Charlottesville, Virginia, United States, 22908
      • Norfolk, Virginia, United States, 23507
        • Recruiting
        • Sentara Norfolk General Hospital
        • Principal Investigator:
          • John K. Plemmons
        • Contact:
          • Site Public Contact
          • Phone Number: 757-388-2406
      • Norfolk, Virginia, United States, 23502
        • Recruiting
        • Sentara Leigh Hospital
        • Contact:
        • Principal Investigator:
          • John K. Plemmons
      • Virginia Beach, Virginia, United States, 23456
        • Recruiting
        • Sentara Princess Anne Hospital
        • Contact:
        • Principal Investigator:
          • John K. Plemmons
    • Washington
      • Seattle, Washington, United States, 98122-4307
        • Recruiting
        • Swedish Medical Center-First Hill
        • Principal Investigator:
          • Alison K. Conlin
        • Contact:
    • West Virginia
      • Morgantown, West Virginia, United States, 26506
        • Recruiting
        • West Virginia University Healthcare
        • Principal Investigator:
          • Cimmie L. Shahan
        • Contact:
    • Wisconsin
      • Appleton, Wisconsin, United States, 54911
        • Recruiting
        • ThedaCare Regional Cancer Center
        • Principal Investigator:
          • Susan Sung
        • Contact:
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Gundersen Lutheran Medical Center
        • Principal Investigator:
          • Andrew D. Prather
        • Contact:
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Hospital and Clinics
        • Principal Investigator:
          • Mai A. Elezaby
        • Contact:
          • Site Public Contact
          • Phone Number: 800-622-8922
      • Marshfield, Wisconsin, United States, 54449
      • Mukwonago, Wisconsin, United States, 53149
        • Recruiting
        • ProHealth D N Greenwald Center
        • Contact:
        • Principal Investigator:
          • Timothy R. Wassenaar
      • Oconomowoc, Wisconsin, United States, 53066
        • Recruiting
        • ProHealth Oconomowoc Memorial Hospital
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:
          • Site Public Contact
          • Phone Number: 262-928-7878
      • Waukesha, Wisconsin, United States, 53188
        • Recruiting
        • UW Cancer Center at ProHealth Care
        • Principal Investigator:
          • Timothy R. Wassenaar
        • Contact:

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

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
Intervention / Treatment
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

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

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

ECOG-ACRIN Cancer Research Group

Collaborators

National Cancer Institute (NCI)
Canadian Cancer Trials Group (CCTG)

Investigators

  • Principal Investigator: Etta Pisano, ECOG-ACRIN Cancer Research Group

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)

September 28, 2017

Primary Completion (Estimated)

December 31, 2030

Study Completion (Estimated)

December 31, 2030

Study Registration Dates

First Submitted

July 5, 2017

First Submitted That Met QC Criteria

July 25, 2017

First Posted (Actual)

July 28, 2017

Study Record Updates

Last Update Posted (Actual)

June 22, 2023

Last Update Submitted That Met QC Criteria

June 21, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Other Study ID 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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