Digital Tomosynthesis Mammography and Digital Mammography in Screening Patients for Breast Cancer
Purpose
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.
Condition
- Breast Screening
Eligibility
- Eligible Ages
- Between 45 Years and 74 Years
- Eligible Genders
- Female
- Accepts Healthy Volunteers
- Yes
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 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 Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Participants will be randomized to either Digital Breast Tomography (TM) or Full Field Digital Mammography (DM)
- Primary Purpose
- Screening
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
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. |
|
|
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. |
|
Recruiting Locations
Birmingham, Alabama 35233
Mobile, Alabama 36607
Site Public Contact
251-435-3942
Phoenix, Arizona 85006
Phoenix, Arizona 85008
Site Public Contact
602-344-5775
Phoenix, Arizona 85054
Site Public Contact
855-776-0015
Little Rock, Arkansas 72205
Site Public Contact
501-686-8274
Los Angeles, California 90033
Los Angeles, California 90033
Site Public Contact
323-865-0451
Modesto, California 95356
San Francisco, California 94110
Aurora, Colorado 80045
Site Public Contact
720-848-0650
Colorado Springs, Colorado 80907
Denver, Colorado 80209
Highlands Ranch, Colorado 80129
Site Public Contact
720-848-0650
Newark, Delaware 19713
Washington, District of Columbia 20007
Site Public Contact
202-444-2223
Jacksonville, Florida 32209
Atlanta, Georgia 30342
Braselton, Georgia 30517
Savannah, Georgia 31405
Honolulu, Hawaii 96813
Site Public Contact
808-545-8548
Boise, Idaho 83706
Boise, Idaho 83712
Bloomington, Illinois 61701
Chicago, Illinois 60612
Site Public Contact
312-864-5204
Danville, Illinois 61832
Danville, Illinois 61832
Decatur, Illinois 62526
Hoopeston, Illinois 60942
Mattoon, Illinois 61938
Normal, Illinois 61761
Urbana, Illinois 61801
Hobart, Indiana 46342
Indianapolis, Indiana 46202
Munster, Indiana 46321
Site Public Contact
219-836-3349
Munster, Indiana 46321
Valparaiso, Indiana 46383
Des Moines, Iowa 50314
Iowa City, Iowa 52242
Site Public Contact
800-237-1225
Owensboro, Kentucky 42303
Baton Rouge, Louisiana 70817
New Orleans, Louisiana 70112
New Orleans, Louisiana 70112
Shreveport, Louisiana 71101
Shreveport, Louisiana 71103
Kensington, Maryland 20895
Site Public Contact
301-816-7218
Boston, Massachusetts 02118
Site Public Contact
617-638-8265
Worcester, Massachusetts 01655
Ann Arbor, Michigan 48106
Ann Arbor, Michigan 48109
Site Public Contact
800-865-1125
Battle Creek, Michigan 49017
Detroit, Michigan 48201
Detroit, Michigan 48202
Grand Rapids, Michigan 49503
Kalamazoo, Michigan 49007
West Bloomfield, Michigan 48322
Duluth, Minnesota 55805
Minneapolis, Minnesota 55415
Rochester, Minnesota 55905
Site Public Contact
855-776-0015
Saint Louis Park, Minnesota 55416
Saint Paul, Minnesota 55101
Thief River Falls, Minnesota 56701
Site Public Contact
605-312-3320
Virginia, Minnesota 55792
Southhaven, Mississippi 38671
Carson City, Nevada 89703
Flemington, New Jersey 08822
Site Public Contact
908-237-2330
New Brunswick, New Jersey 08901
Sewell, New Jersey 08080
Albuquerque, New Mexico 87106
Bronx, New York 10461
New York, New York 10032
Rochester, New York 14642
Site Public Contact
585-275-5830
Chapel Hill, North Carolina 27599
Durham, North Carolina 27710
Site Public Contact
888-275-3853
Hillsborough, North Carolina 27278
Winston-Salem, North Carolina 27157
Site Public Contact
336-713-6771
Bismarck, North Dakota 58501
Fargo, North Dakota 58103
Site Public Contact
605-312-3320
Beachwood, Ohio 44122
Canton, Ohio 44710
Cincinnati, Ohio 45219
Cleveland, Ohio 44195
Columbus, Ohio 43210
Hershey, Pennsylvania 17033-0850
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19107
Philadelphia, Pennsylvania 19111
Site Public Contact
215-728-4790
Pittsburgh, Pennsylvania 15212
Site Public Contact
877-284-2000
Wexford, Pennsylvania 15090
Charleston, South Carolina 29425
Columbia, South Carolina 29203
Site Public Contact
864-241-6251
Greenville, South Carolina 29605
Site Public Contact
864-241-6251
Mount Pleasant, South Carolina 29464
Spartanburg, South Carolina 29303
Spartanburg, South Carolina 29307
Site Public Contact
864-560-6812
Memphis, Tennessee 38120
Nashville, Tennessee 37204
Site Public Contact
800-811-8480
Nashville, Tennessee 37232
Site Public Contact
800-811-8480
Dallas, Texas 75390
Houston, Texas 77030
Houston, Texas 77030
Site Public Contact
713-792-3245
Houston, Texas 77098
Site Public Contact
713-704-9567
Charlottesville, Virginia 22908
Midlothian, Virginia 23113
Norfolk, Virginia 23502
Norfolk, Virginia 23507
Site Public Contact
757-388-2406
Virginia Beach, Virginia 23456
Seattle, Washington 98122
Appleton, Wisconsin 54911
La Crosse, Wisconsin 54601
Madison, Wisconsin 53792
Marshfield, Wisconsin 54449
Mukwonago, Wisconsin 53149
Oconomowoc, Wisconsin 53066
Site Public Contact
262-928-7878
Superior, Wisconsin 54880
Site Public Contact
701-364-6272
Waukesha, Wisconsin 53188
San Juan, Puerto Rico 00936
Site Public Contact
787-763-1296
More Details
- NCT ID
- NCT03233191
- Status
- Recruiting
- Sponsor
- ECOG-ACRIN Cancer Research Group
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.