Breast Cancer

EA1151 / TMIST



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

STATUS: Active


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.
  • Patients must be women age 45 or older and under age 75 at the time of study entry

  • 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

  • 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 four risk factors: ** Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or ** At least one benign breast biopsy with a diagnosis of lobular carcinoma in situ (LCIS) or atypia of any kind (atypical ductal hyperplasia, atypical lobular hyperplasia, atypical hyperplasia not otherwise specified [NOS], or intraductal papilloma with atypia), or ** Family history of breast cancer (first degree relative with breast cancer) or family history of breast cancer is not known, or, participant 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 three risk factors: ** Dense breasts (BIRADS density categories c-heterogeneously dense or d-extremely dense), or ** At least one benign breast biopsy with a diagnosis of LCIS or atypia of any kind (atypical ductal hyperplasia, atypical lobular hyperplasia, atypical hyperplasia NOS, or intraductal papilloma with atypia), or ** Currently on hormone therapy *** For this study we define hormone therapies as those that increase breast cancer risk, including: estrogen, progesterone, estrogen/progesterone analogs, or hormonal birth control prescribed by a doctor, and include hormones in oral contraceptives, patch, gel, etc. BUT, for this study; soy use is not considered 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 bilateral oophorectomy with either hysterectomy or endometrial ablation will be considered postmenopausal; women who no longer have menses due to either hysterectomy or endometrial ablation, and who have at least one ovary 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 for whom a prior mammogram interpretation is not available, breast density will be determined by the radiologistโ€™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 2D 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, or by radiologist review of prior imaging; * NOTE: If the latter method is used, a signed, dated attestation by the radiologist indicating the resulting determination must be kept as a record and made available for monitoring/auditing * All other risk factors used to determine patient eligibility for annual or biennial screening will be determined by subject self-report

  • Patients must not have new symptoms or signs of benign or malignant breast disease (e.g., bloody or clear nipple discharge, breast lump) based on physician physical exam or self breast exam that have not been previously worked up with imaging; patients with physiologic nipple discharge or 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 currently have breast enhancements (e.g., implants or radiopaque injections)

Argentina
Buenos Aires
CERIM
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Canada
British Columbia
Vancouver
BCCA-Vancouver Cancer Centre
Contact: Site Public Contact

Ontario
London
Saint Joseph's Health Care London
Contact: Site Public Contact
Email: patientrelations@sjhc.london.on.ca

Ottawa
Ottawa Hospital and Cancer Center-General Campus
Contact: Site Public Contact

Toronto
Mount Sinai Hospital
Contact: Site Public Contact

Odette Cancer Centre- Sunnybrook Health Sciences Centre
Contact: Site Public Contact

Quebec
Montreal
Hopital Du Sacre-Coeur de Montreal
Contact: Site Public Contact

Quebec City
CHU de Quebec-Hopital du Saint-Sacrement (HSS)
Contact: Site Public Contact
Email: jbegin@uresp.ulaval.ca

Italy
Treviso
Ospedale Ca Foncello di Treviso - ULSS 2 Marca Trevigiana
Contact: Site Public Contact
Email: claudiamaria.weiss@aulss2.veneto.it

Korea, Republic of
Gyeonggi-do
Goyang-si
National Cancer Center-Korea
Contact: Site Public Contact

Peru
Lima
Oncosalud S.A.C.
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

United States
AL
Birmingham
University of Alabama at Birmingham Cancer Center
Contact: Site Public Contact
Email: tmyrick@uab.edu

Mobile
Mobile Infirmary Medical Center
Contact: Site Public Contact

AR
Little Rock
University of Arkansas for Medical Sciences
Contact: Site Public Contact

AZ
Phoenix
Banner-University Medical Center Phoenix
Contact: Site Public Contact
Email: BannerResearch@bannerhealth.com

Mayo Clinic Hospital in Arizona
Contact: Site Public Contact

University of Arizona College of Medicine Phoenix
Contact: Site Public Contact
Email: atvalencia@email.arizona.edu

Valleywise Comprehensive Health Center - Phoenix
Contact: Site Public Contact

Scottsdale
Scottsdale Medical Imaging Limited
Contact: Site Public Contact
Email: investigator@esmil.com

CA
Bakersfield
Kern Radiology Medical Group Inc
Contact: Site Public Contact

Los Angeles
Los Angeles County-USC Medical Center
Contact: Site Public Contact

USC / Norris Comprehensive Cancer Center
Contact: Site Public Contact

Modesto
Kaiser Permanente-Modesto
Contact: Site Public Contact
Email: Kpoct@kp.org

San Francisco
Zuckerberg San Francisco General Hospital
Contact: Site Public Contact
Email: Paul.Couey@ucsf.edu

CO
Aurora
University of Colorado Hospital
Contact: Site Public Contact

Colorado Springs
Penrose-Saint Francis Healthcare
Contact: Site Public Contact
Email: ResearchTracking@Centura.Org

Denver
The Women's Imaging Center
Contact: Site Public Contact
Email: info@westernstatesncorp.org

Englewood
Radiology Imaging Associates
Contact: Site Public Contact
Email: research@riaco.com

Highlands Ranch
UCHealth Highlands Ranch Hospital
Contact: Site Public Contact

Lone Tree
UCHealth Lone Tree Health Center
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

DC
Washington
MedStar Georgetown University Hospital
Contact: Site Public Contact

DE
Newark
Helen F Graham Cancer Center
Contact: Site Public Contact
Email: mhayden@christianacare.org

FL
Jacksonville
University of Florida Health Science Center - Jacksonville
Contact: Site Public Contact
Email: trials@cancer.ufl.edu

GA
Atlanta
Northside Hospital
Contact: Site Public Contact
Email: ClinicalTrials@northside.com

Braselton
Northeast Georgia Medical Center Braselton
Contact: Site Public Contact
Email: cancerpatient.navigator@nghs.com

Savannah
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Contact: Site Public Contact
Email: underberga@sjchs.org

HI
Honolulu
Queen's Medical Center
Contact: Site Public Contact

IA
Des Moines
Mercy Medical Center - Des Moines
Contact: Site Public Contact
Email: cancerresearch@mercydesmoines.org

Iowa City
University of Iowa/Holden Comprehensive Cancer Center
Contact: Site Public Contact

ID
Boise
Saint Alphonsus Cancer Care Center-Boise
Contact: Site Public Contact
Email: stephanie.couch@stjoeshealth.org

Saint Luke's Cancer Institute - Boise
Contact: Site Public Contact
Email: eslinget@slhs.org

IL
Chicago
John H Stroger Jr Hospital of Cook County
Contact: Site Public Contact

Danville
Carle on Fairchild
Contact: Site Public Contact
Email: Research@carle.com

Decatur
Decatur Memorial Hospital
Contact: Site Public Contact
Email: morganthaler.jodi@mhsil.com

Hoopeston
Carle Hoopeston Regional Health Center
Contact: Site Public Contact
Email: Research@carle.com

Mattoon
Carle Physician Group-Mattoon/Charleston
Contact: Site Public Contact
Email: Research@carle.com

Urbana
Carle Cancer Center
Contact: Site Public Contact
Email: Research@carle.com

IN
Hobart
Saint Mary Medical Center
Contact: Site Public Contact
Email: ecog.rss@jimmy.harvard.edu

Indianapolis
Indiana University/Melvin and Bren Simon Cancer Center
Contact: Site Public Contact
Email: iutrials@iu.edu

Munster
The Community Hospital
Contact: Site Public Contact

Women's Diagnostic Center - Munster
Contact: Site Public Contact
Email: mnicholson@comhs.org

KY
Owensboro
Owensboro Health Mitchell Memorial Cancer Center
Contact: Site Public Contact
Email: vanissa.sorrels@owensborohealth.org

LA
Baton Rouge
Mary Bird Perkins Cancer Center
Contact: Site Public Contact
Email: clinicalresearch@marybird.com

Woman's Hospital
Contact: Site Public Contact
Email: Clinicalreserach@marybird.com

New Orleans
Tulane University Health Sciences Center
Contact: Site Public Contact

University Medical Center New Orleans
Contact: Site Public Contact
Email: emede1@lsuhsc.edu

Shreveport
LSU Health Sciences Center at Shreveport
Contact: Site Public Contact
Email: LPost@lsuhsc.edu

Ochsner LSU Health Saint Mary's Medical Center
Contact: Site Public Contact
Email: LPost@lsuhsc.edu

MA
Boston
Boston Medical Center
Contact: Site Public Contact

Worcester
UMass Memorial Medical Center - University Campus
Contact: Site Public Contact
Email: cancer.research@umassmed.edu

MD
Kensington
Kaiser Permanente - Kensington Medical Center
Contact: Site Public Contact

MI
Ann Arbor
Saint Joseph Mercy Hospital
Contact: Site Public Contact
Email: MCRCwebsitecontactform@stjoeshealth.org

University of Michigan Comprehensive Cancer Center
Contact: Site Public Contact

Battle Creek
Bronson Battle Creek
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Detroit
Henry Ford Hospital
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

Wayne State University/Karmanos Cancer Institute
Contact: Site Public Contact
Email: ctoadmin@karmanos.org

Farmington Hills
Weisberg Cancer Treatment Center
Contact: Site Public Contact
Email: ctoadmin@karmanos.org

Grand Rapids
Spectrum Health at Butterworth Campus
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

Kalamazoo
West Michigan Cancer Center
Contact: Site Public Contact
Email: crcwm-regulatory@crcwm.org

West Bloomfield
Henry Ford West Bloomfield Hospital
Contact: Site Public Contact
Email: CTOResearch@hfhs.org

MN
Duluth
Essentia Health Cancer Center
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

Minneapolis
Hennepin County Medical Center
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

Rochester
Mayo Clinic in Rochester
Contact: Site Public Contact

Saint Louis Park
Park Nicollet Clinic - Saint Louis Park
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

Saint Paul
Regions Hospital
Contact: Site Public Contact
Email: mmcorc@healthpartners.com

Thief River Falls
Sanford Thief River Falls Medical Center
Contact: Site Public Contact

Virginia
Essentia Health Virginia Clinic
Contact: Site Public Contact
Email: CancerTrials@EssentiaHealth.org

MS
Southhaven
Baptist Memorial Hospital and Cancer Center-Desoto
Contact: Site Public Contact
Email: BCCclintrials@bmhcc.org

NC
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Contact: Site Public Contact
Email: cancerclinicaltrials@med.unc.edu

Durham
Duke University Medical Center
Contact: Site Public Contact

Hillsborough
University of North Carolina-Hillsborough Campus
Contact: Site Public Contact
Email: cancerclinicaltrials@med.unc.edu

Winston-Salem
Wake Forest University Health Sciences
Contact: Site Public Contact

ND
Bismarck
Sanford Bismarck Medical Center
Contact: Site Public Contact
Email: OncologyClinicalTrialsFargo@sanfordhealth.org

Fargo
Southpointe-Sanford Medical Center Fargo
Contact: Site Public Contact

NJ
Flemington
Hunterdon Medical Center
Contact: Site Public Contact

New Brunswick
Saint Peter's University Hospital
Contact: Site Public Contact
Email: kcovert@saintpetersuh.com

Red Bank
Riverview Medical Center/Booker Cancer Center
Contact: Site Public Contact

Sewell
Sidney Kimmel Cancer Center Washington Township
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

NM
Albuquerque
University of New Mexico Cancer Center
Contact: Site Public Contact
Email: LByatt@nmcca.org

NV
Carson City
Carson Tahoe Regional Medical Center
Contact: Site Public Contact
Email: research@sncrf.org

NY
Bronx
Montefiore Medical Center-Einstein Campus
Contact: Site Public Contact
Email: eskwak@montefiore.org

Montefiore Medical Center-Weiler Hospital
Contact: Site Public Contact
Email: eskwak@montefiore.org

Elmira
Arnot Ogden Medical Center/Falck Cancer Center
Contact: Site Public Contact

New York
Memorial Sloan Kettering Cancer Center
Contact: Site Public Contact

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Contact: Site Public Contact
Email: nr2616@cumc.columbia.edu

NYP/Weill Cornell Medical Center
Contact: Site Public Contact

Rochester
University of Rochester
Contact: Site Public Contact

OH
Canton
Aultman Health Foundation
Contact: Site Public Contact
Email: ClinicalReserachDept@aultman.com

Cincinnati
University of Cincinnati Cancer Center-UC Medical Center
Contact: Site Public Contact
Email: cancer@uchealth.com

Cleveland
Cleveland Clinic Foundation
Contact: Site Public Contact
Email: TaussigResearch@ccf.org

Columbus
Ohio State University Comprehensive Cancer Center
Contact: Site Public Contact
Email: Jamesline@osumc.edu

PA
Easton
Easton Hospital
Contact: Site Public Contact

Hershey
Penn State Milton S Hershey Medical Center
Contact: Site Public Contact
Email: CTO@hmc.psu.edu

Philadelphia
Fox Chase Cancer Center
Contact: Site Public Contact

Pennsylvania Hospital
Contact: Site Public Contact

Thomas Jefferson University Hospital
Contact: Site Public Contact
Email: ONCTrialNow@jefferson.edu

Pittsburgh
Allegheny General Hospital
Contact: Site Public Contact

Wexford
Wexford Health and Wellness Pavilion
Contact: Site Public Contact
Email: Dawnmarie.DeFazio@ahn.org

PR
San Juan
San Juan City Hospital
Contact: Site Public Contact

SC
Charleston
Medical University of South Carolina
Contact: Site Public Contact
Email: hcc-clinical-trials@musc.edu

Columbia
Prisma Health Richland Hospital
Contact: Site Public Contact

Greenville
Prisma Health Greenville Memorial Hospital
Contact: Site Public Contact

Mount Pleasant
MUSC Health East Cooper
Contact: Site Public Contact
Email: hcc-clinical-trials@musc.edu

Spartanburg
Spartanburg Medical Center
Contact: Site Public Contact
Email: kmertz-rivera@gibbscc.org

Spartanburg Medical Center - Mary Black Campus
Contact: Site Public Contact

TN
Knoxville
University of Tennessee - Knoxville
Contact: Site Public Contact

Memphis
Baptist Memorial Hospital and Cancer Center-Memphis
Contact: Site Public Contact
Email: BCCclintrials@bmhcc.org

Baptist Memorial Hospital for Women
Contact: Site Public Contact
Email: BCCclintrials@bmhcc.org

Nashville
Vanderbilt Breast Center at One Hundred Oaks
Contact: Site Public Contact

Vanderbilt University/Ingram Cancer Center
Contact: Site Public Contact

TX
Dallas
UT Southwestern/Simmons Cancer Center-Dallas
Contact: Site Public Contact
Email: canceranswerline@UTSouthwestern.edu

Houston
M D Anderson Cancer Center
Contact: Site Public Contact
Email: askmdanderson@mdanderson.org

Memorial Hermann Texas Medical Center
Contact: Site Public Contact

San Antonio
University Hospital
Contact: Site Public Contact
Email: evelyn.swenson-britt@uhs-sa.com

VA
Charlottesville
University of Virginia Cancer Center
Contact: Site Public Contact
Email: uvacancertrials@hscmail.mcc.virginia.edu

Midlothian
Bon Secours Westchester Emergency Center
Contact: Site Public Contact
Email: Jaime_scott@bshsi.org

Norfolk
Sentara Leigh Hospital
Contact: Site Public Contact
Email: djoverto@sentara.com

Sentara Norfolk General Hospital
Contact: Site Public Contact

Virginia Beach
Sentara Princess Anne Hospital
Contact: Site Public Contact
Email: djoverto@sentara.com

WI
Appleton
ThedaCare Regional Cancer Center
Contact: Site Public Contact
Email: ResearchDept@thedacare.org

La Crosse
Gundersen Lutheran Medical Center
Contact: Site Public Contact
Email: cancerctr@gundersenhealth.org

Madison
University of Wisconsin Carbone Cancer Center
Contact: Site Public Contact

Marshfield
Marshfield Medical Center-Marshfield
Contact: Site Public Contact
Email: oncology.clinical.trials@marshfieldresearch.org

Mukwonago
ProHealth D N Greenwald Center
Contact: Site Public Contact
Email: research.institute@phci.org

Oconomowoc
ProHealth Oconomowoc Memorial Hospital
Contact: Site Public Contact

Superior
Essentia Health Saint Mary's Hospital - Superior
Contact: Site Public Contact

Waukesha
UW Cancer Center at ProHealth Care
Contact: Site Public Contact
Email: Chanda.miller@phci.org

WV
Morgantown
West Virginia University Healthcare
Contact: Site Public Contact
Email: cancertrialsinfo@hsc.wvu.edu

PRIMARY OBJECTIVE:
I. To compare the cumulative proportions of participants reaching the primary endpoint in the two study arms, using time-to-advanced cancer measured from randomization.

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 tomosynthesis (TM) and digital mammography (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: p53 mutant-like or wild-type-like according to a validated p53 dependent signature; immune subtypes using a multigene signature of immune markers; deoxyribonucleic acid (DNA) repair phenotypes using a multigene signature of DNA repair genes; and a research version the 21-gene recurrence score in the two arms, overall and stratified on (a) whether cancers were detected through screening or as interval cancers, and (b) 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, p53 mutant-like or wild-type like according to a validated p53-dependent signature, immune active or inactive using a multi-gene immune signature, DNA repair high or low a DNA repair signature, and high or low/medium (med) risk based on the 21- gene recurrence assay.
X. To assess the agreement between local and expert study pathologists for all breast lesions (benign and malignant) biopsied during the study.
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 as described in Aim II.
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 3-8 years after study entry, dependent on when patients enroll.

Interactive content above is from the official study record on the National Cancer Institute website, cancer.gov.


The ECOG-ACRIN Cancer Research Group designed this trial and is conducting it with funding from the National Cancer Institute through its NCI Community Oncology Research Program (NCORP) and National Clinical Trials Network (NCTN).


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ECOG-ACRIN Cancer Research Group