Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
Description
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.
Eligibility Criteria
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 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 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 ** 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 two 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
- 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 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 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
Locations & Contacts
Alabama
Birmingham
Status: Active
Contact: Site Public Contact
Phone: 205-934-0220
Email: tmyrick@uab.edu
Mobile
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Phone: 251-435-3942
Arizona
Phoenix
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Phone: 855-776-0015
Status: Active
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Phone: 520-780-8241
Email: atvalencia@email.arizona.edu
Status: Active
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Phone: 602-344-5775
Scottsdale
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Phone: 480-425-4170
Email: investigator@esmil.com
Arkansas
Little Rock
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Phone: 501-686-8274
California
Bakersfield
Status: Temporarily closed to accrual
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Los Angeles
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Phone: 323-865-0451
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San Francisco
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Colorado
Aurora
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Phone: 720-848-0650
Colorado Springs
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Phone: 308-398-6518
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Denver
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Phone: 303-777-2663
Email: ccrp@co-cancerresearch.org
Englewood
Status: Temporarily closed to accrual
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Highlands Ranch
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Delaware
Newark
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Georgia
Atlanta
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Phone: 404-303-3355
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Braselton
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Savannah
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Hawaii
Honolulu
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Idaho
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Illinois
Chicago
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Danville
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Decatur
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Urbana
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Indiana
Indianapolis
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Iowa
Des Moines
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Louisiana
Baton Rouge
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New Orleans
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Shreveport
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Maryland
Kensington
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Massachusetts
Boston
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Worcester
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Michigan
Ann Arbor
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Phone: 734-712-3671
Email: stephanie.couch@stjoeshealth.org
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Battle Creek
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Phone: 616-391-1230
Email: crcwm-regulatory@crcwm.org
Detroit
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Phone: 313-916-3721
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Farmington Hills
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Phone: 313-576-9790
Email: ctoadmin@karmanos.org
Grand Rapids
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Phone: 616-391-1230
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Kalamazoo
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West Bloomfield
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Phone: 313-916-3721
Email: CTOResearch@hfhs.org
Minnesota
Duluth
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Phone: 218-786-3308
Email: CancerTrials@EssentiaHealth.org
Minneapolis
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Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Rochester
Status: Active
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Phone: 855-776-0015
Saint Louis Park
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Phone: 952-993-1517
Email: mmcorc@healthpartners.com
Saint Paul
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Phone: 952-993-1517
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Nevada
Carson City
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New Jersey
Flemington
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Phone: 888-788-1260
New Brunswick
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Red Bank
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Phone: 732-530-2382
New Mexico
Albuquerque
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Phone: 505-925-0366
Email: LByatt@nmcca.org
New York
Bronx
Status: Active
Contact: Site Public Contact
Phone: 718-379-6866
Email: aaraiza@montefiore.org
Status: Temporarily closed to accrual
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Elmira
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Phone: 607-271-7000
New York
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Phone: 212-639-7592
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Email: nr2616@cumc.columbia.edu
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North Carolina
Chapel Hill
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Phone: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu
Durham
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Hillsborough
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Email: cancerclinicaltrials@med.unc.edu
Winston-Salem
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Phone: 336-713-6771
North Dakota
Bismarck
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Phone: 701-323-5760
Email: OncologyClinicalTrialsFargo@sanfordhealth.org
Ohio
Canton
Status: Active
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Phone: 330-363-7274
Email: ClinicalReserachDept@aultman.com
Cincinnati
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Phone: 513-558-4553
Email: uchealthnews@uc.edu
Cleveland
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Columbus
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Email: Jamesline@osumc.edu
Pennsylvania
Easton
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Phone: 610-250-4000
Hershey
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Philadelphia
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Pittsburgh
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Wexford
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Puerto Rico
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South Carolina
Mount Pleasant
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Phone: 843-792-9321
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Spartanburg
Status: Active
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Phone: 864-560-6104
Email: kmertz-rivera@gibbscc.org
Tennessee
Memphis
Status: Temporarily closed to accrual
Contact: Site Public Contact
Phone: 901-226-1366
Email: BCCclintrials@bmhcc.org
Status: Active
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Phone: 901-226-1366
Email: BCCclintrials@bmhcc.org
Nashville
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Phone: 800-811-8480
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Texas
Dallas
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Phone: 214-648-7097
Email: canceranswerline@UTSouthwestern.edu
Houston
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Phone: 877-632-6789
Email: askmdanderson@mdanderson.org
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Virginia
Charlottesville
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Phone: 434-243-6303
Email: PAS9E@virginia.edu
Norfolk
Status: Active
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Phone: 757-388-5109
Email: djoverto@sentara.com
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Virginia Beach
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Washington
Seattle
Status: Active
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Phone: 206-215-3086
Email: PCRC-NCORP@Swedish.org
West Virginia
Morgantown
Status: Active
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Phone: 304-293-7374
Email: cancertrialsinfo@hsc.wvu.edu
Wisconsin
Appleton
Status: Active
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Phone: 920-364-3605
Email: Noreen.Wynn@thedacare.org
La Crosse
Status: Active
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Phone: 608-775-2385
Email: cancerctr@gundersenhealth.org
Madison
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Phone: 800-622-8922
Marshfield
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Contact: Site Public Contact
Phone: 800-782-8581
Email: oncology.clinical.trials@marshfieldresearch.org
Mukwonago
Status: Active
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Email: research.institute@phci.org
Oconomowoc
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Phone: 262-928-7878
Waukesha
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Email: Chanda.miller@phci.org
British Columbia
Vancouver
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Phone: 888-939-3333
Ontario
London
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Ottawa
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Toronto
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Quebec
Montreal
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Quebec City
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Argentina
Buenos Aires
Trial Objectives and Outline
PRIMARY OBJECTIVES:
I. To compare the proportions of participants in the tomosynthesis (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 4.5-8 years after study entry.
Trial Phase & Type
Screening
Lead Organization
Lead Organization
ECOG-ACRIN Cancer Research Group
Principal Investigator
Etta D. Pisano