Abbreviated Breast MRI and Digital Tomosynthesis Mammography in Screening Women With Dense Breasts

Comparison of Abbreviated Breast MRI and Digital Breast Tomosynthesis in Breast Cancer Screening in Women With Dense Breasts

This randomized phase II trial studies how well abbreviated breast magnetic resonance imaging (MRI) and digital tomosynthesis mammography work in detecting cancer in women with dense breasts. Abbreviated breast MRI is a low cost procedure in which radio waves and a powerful magnet linked to a computer and used to create detailed pictures of the breast in less than 10 minutes. These pictures can show the difference between normal and diseased tissue. Digital tomosynthesis mammography is a procedure that uses multiple x-rays pictures of each breast to produce a 3-dimensional rendering of the entire breast. Combined screening with abbreviated breast MRI and digital tomosynthesis mammography may be a better method to screen women with dense breasts.

Study Overview

• Status: Active, not recruiting
• Conditions: Asymptomatic
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Diagnostic test: Contrast-enhanced Magnetic Resonance Imaging; Diagnostic test: Digital Tomosynthesis Mammography

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the rates of detection of invasive cancers between the initial abbreviated breast (AB)-magnetic resonance (MR) and digital tomosynthesis mammography (DBT).

SECONDARY OBJECTIVES:

I. To compare the positive predictive value (PPV) of biopsies, call back rates, and short-term follow up rates after AB-MR and DBT on both the initial and 1 year follow up studies.

II. To estimate and compare the sensitivity and specificity of AB-MR and DBT, using the 1 year follow up to define a reference standard.

III. To compare patient-reported short-term quality of life related to diagnostic testing with AB-MR and DBT using the Testing Morbidities Index.

IV. To compare willingness to return for testing with AB-MRI versus (vs) DBT within the recommended screening interval and explore factors associated with willingness to return for screening.

V. To compare the tumor biologies of invasive cancers and ductal carcinoma in situ (DCIS) detected on AB-MR and DBT.

VI. To estimate the incident cancer rate during 3 years following the year-1 AB-MR/DBT when patients return to standard screening.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A (DBT, AB-MR): Participants undergo DBT followed by AB-MR for under 10 minutes on the same day or within 24 hours at baseline and then after 1 year.

ARM B (AB-MR, DBT): Participants undergo AB-MR for under 10 minutes followed by DBT on the same day or within 24 hours at baseline and then after 1 year.

After completion of study, patients are followed up at every 6 months for 3 years.

• Study Type: Interventional
• Enrollment (Actual): 1516
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • Rwth Klinikum Aachen
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Pasadena, California, United States, 91105
      • Huntington Memorial Hospital
  • Colorado
    • Denver, Colorado, United States, 80209
      • The Women's Imaging Center
    • Englewood, Colorado, United States, 80112
      • Radiology Imaging Associates
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Norwalk Hospital
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33173
      • Diagnostic Center for Women LLC
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Springfield, Illinois, United States, 62781
      • Clinical Radiologists SC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University/Melvin and Bren Simon Cancer Center
    • Munster, Indiana, United States, 46321
      • The Community Hospital
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Oncology Associates at Mercy Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital and Medical Center
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Red Bank, New Jersey, United States, 07701
      • Riverview Medical Center/Booker Cancer Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center-Einstein Campus
    • Bronx, New York, United States, 10467-2490
      • Montefiore Medical Center - Moses Campus
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Winston-Salem, North Carolina, United States, 27103
      • Novant Health Forsyth Medical Center
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19103
      • ECOG-ACRIN Cancer Research Group
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University/Ingram Cancer Center
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Breast Center at One Hundred Oaks
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
  • Utah
    • Farmington, Utah, United States, 84025
      • Farmington Health Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • South Jordan, Utah, United States, 84009
      • South Jordan Health Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Charlottesville, Virginia, United States, 22901
      • Sentara Martha Jefferson Hospital
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Norfolk, Virginia, United States, 23502
      • Sentara Leigh Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • ThedaCare Regional Cancer Center
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital and Clinics
    • Mukwonago, Wisconsin, United States, 53149
      • ProHealth D N Greenwald Center
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care
    • Waukesha, Wisconsin, United States, 53188
      • ProHealth Waukesha Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Patents must be scheduled for routine screening DBT
• Women must not be pregnant or breast-feeding; all females of childbearing potential who are uncertain if they could be pregnant or may be pregnant or as per local site standard of practice in women undergoing DBT and MRI must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Women of childbearing potential must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the following year until the year 1 AB-MR and DBT studies are performed
• Patient?s breast density must be known; patients must have mammographically dense breasts, American College of Radiology [ACR] Breast Imaging [BI]- Reporting and Data System Atlas (RADS) lexicon categories c or d (heterogeneous or extreme fibroglandular tissue) on their most-recent prior screening
• Patient must be asymptomatic for breast disease and undergoing routine screening
• Patient must have no known breast cancer (DCIS or invasive cancer), not currently undergoing treatment for breast cancer, or planning surgery for a high risk lesion (atypical ductal breast hyperplasia [ADH], atypical lobular breast hyperplasia [ALH], lobular breast carcinoma in situ [LCIS], papilloma, radial scar)
• Patient must not be taking chemoprevention for breast cancer
• Patient must not have undergone breast ultrasound within 12 months prior to randomization
• Patient must not have previously had a breast MRI
• Patient must not have previously had molecular breast imaging (MBI, multiplexed ion beam imaging [MIBI])
• Patient must agree to not undergo screening ultrasound (of breast) for the duration of the 1 year study period
• Patient must not be suspected of being at high-risk for breast cancer, as defined by the American Cancer Society (ACS) breast MR screening recommendations (lifetime risk of >= 20-25%)

• Patient must be able to undergo breast MRI with contrast enhancement; patients unable to undergo breast MRI with contrast enhancement for any reason are ineligible

  • No history of untreatable claustrophobia
  • No presence of non MR compatible metallic objects or metallic objects that, in the opinion of the radiologist, would make MRI a contraindication
  • No history of sickle cell disease
  • No contraindication to intravenous contrast administration
  • No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance
  • No known or suspected renal impairment; requirements for glomerular filtration rate (GFR) prior to MRI as determined by local site standard practice
  • Weight less than or equal to the MRI table limit
  • No women who have had prior contrast enhanced mammography (contrast enhanced spectral mammography [CESM] or contrast enhanced digital mammography [CEDM])
  • No women who have breast prosthetic implants (silicone or saline) Exclusion Criteria

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A (DBT, AB-MR); Participants undergo DBT followed by AB-MR for under 10 minutes on the same day or within 24 hours at baseline and then after 1 year.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Diagnostic test: Contrast-enhanced Magnetic Resonance Imaging; Undergo AB-MR; Other Names: CONTRAST ENHANCED MRI; Contrast-enhanced MRI; Diagnostic test: Digital Tomosynthesis Mammography; Undergo DBT; Other Names: DBT; Digital Breast Tomosynthesis; Digital Tomosynthesis of the Breast
Experimental: Arm B (AB-MR, DBT); Participants undergo AB-MR for under 10 minutes followed by DBT on the same day or within 24 hours at baseline and then after 1year.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Diagnostic test: Contrast-enhanced Magnetic Resonance Imaging; Undergo AB-MR; Other Names: CONTRAST ENHANCED MRI; Contrast-enhanced MRI; Diagnostic test: Digital Tomosynthesis Mammography; Undergo DBT; 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
Screen-detected Invasive Cancer Verified by Pathology	For each modality, the detection rate of invasive cancers is defined as the proportion of participants who had an invasive cancer detected by the modality at baseline and verified by pathology versus the total number of participants. In the out come measures table below, these proportions will be automatically calculated, multiplied by 100, and be presented as percentages (%).	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prediction of Breast Cancer (Sensitivity and Specificity)	Reference standard positive (RS+): breast cancer (invasive or DCIS) detected on the year 0 screening or reported at any time from the year 0 to the year 1 screening. Reference standard negative (RS-): No breast cancer reported at any time from the year 0 to the year 1 screen. Incomplete: No Year 1 imaging, and <11 months of patient follow-up (<330 days) after year 0 screen Positive Test (T+) is defined as the imaging modality result is positive (BI-RADS 3-5), and the location of the finding is matches the location of the cancer indicated by the reference standard. Negative Test (T-) will be estimated as the fraction of reference standard negative subjects for whom the imaging modality result was negative (BI-RADS 1-2). 95% confidence intervals for the sensitivity and specificity of each modality calculated using the Wilson method.	Baseline to up to 1 year
Positive Predictive Value (PPV) of Biopsies	Test Positive (T+): Biopsy recommended by imaging, defined as patients with at least one lesion rated BI-RADS 4 or 5 on image interpretation. Reference Standard Positive (RS+): Pathologically confirmed DCIS or invasive disease resultant from a positive test. The 95% confidence interval for PPV of biopsy for each modality were derived from the GEE model using the appropriate estimable contrasts with robust standard errors	Baseline to up to 1 year
Call Back/Additional Imaging/Short-term Follow Rates for DBT and AB-MR	For DBT: DBT: Call back is defined as having additional views or targeted ultrasound to evaluate DBT findings DBT: short term follow up (STFU) is defined as having at least one lesion rated BI-RADS 3 on DBT DBT: Additional imaging recommendation is defined as having either call back or STFU For AB-MR: Ab-MR: Call back does not apply to AB-MR and will not be evaluated Ab-MR: Short Term Follow-up (STFU) is defined as having at least one lesion rated BI-RADS 3 on AB-MR Ab-MR: Additional imaging recommendation is defined as having a STFU	Baseline
Incident Cancer Rate	Breast cancer incidence will be estimated. Person-years will be measured.	Up to 3 years
Factors Associated With Willingness to Return for Screening	Polytomous logistic regression will be used to examine factors associated with willingness to return, including screen result, cancer status, and demographic characteristics.	Up to 1 year
Willingness to Return for Testing With Abbreviated Breast-magnetic Resonance (MR) Versus Digital Tomosynthesis Mammography (DBT)	The proportions of participants willing to return for screening with either test, AB-MRI only, DBT only, or not willing to return for either test will be estimated.	Up to 1 year
Change in Patient-reported Short-term Quality of Life Related to Diagnostic Testing	Testing Morbidities Index (TMI) scores [0 (worst) to 100 (best) scale] will be computed for abbreviated breast-magnetic resonance (MR) and digital tomosynthesis mammography (DBT) after the baseline screen.	Baseline to up to 1 year
Ductal Carcinoma in Situ (DCIS) Detected on Abbreviated Breast-magnetic Resonance (MR) and Digital Tomosynthesis Mammography (DBT)	Descriptive Analyses presenting the the distributions of Oncotype-DCIS scores by modality A low risk score is less than 39, and a high risk score is 55 or higher. A score of 39 to 54 is intermediate risk.	Up to 1 year
Tumor Biologies of Invasive Cancers and Ductal Carcinoma in Situ (DCIS) Detected on AB-MR and DBT	For all invasive cancers detected during the study period, the NanoString PAM50 will be performed. The frequencies of cancer types determined by the NanoString analysis will be tabulated and compared. For DCIS, if the Oncotype-DCIS score was performed, the distributions of scores will be tabulated and compared.	end of study

Collaborators and Investigators

• Sponsor: ECOG-ACRIN Cancer Research Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Christopher Comstock, ECOG-ACRIN Cancer Research Group

Publications and helpful links

General Publications

• Comstock CE, Gatsonis C, Newstead GM, Snyder BS, Gareen IF, Bergin JT, Rahbar H, Sung JS, Jacobs C, Harvey JA, Nicholson MH, Ward RC, Holt J, Prather A, Miller KD, Schnall MD, Kuhl CK. Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening. JAMA. 2020 Feb 25;323(8):746-756. doi: 10.1001/jama.2020.0572. Erratum In: JAMA. 2020 Mar 24;323(12):1194.

Helpful Links

• Primary Manuscript

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2016
• Primary Completion (Actual): January 23, 2020
• Study Completion (Estimated): January 31, 2024

Study Registration Dates

• First Submitted: October 12, 2016
• First Submitted That Met QC Criteria: October 13, 2016
• First Posted (Estimated): October 14, 2016

Study Record Updates

• Last Update Posted (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: EA1141 (Other Identifier: CTEP); UG1CA189828 (U.S. NIH Grant/Contract); NCI-2016-00252 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); s16-01825 (Other Identifier: Other); ECOG-ACRIN-EA1141 (Other Identifier: DCP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Safe harbor de-identified data corresponding to publications will be shared upon request
• IPD Sharing Time Frame: With publication
• IPD Sharing Access Criteria: All requests will require a statistical plan and justification. Approved requests will require a DUA.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes