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Breast Ultrasound and Mammography in Screening Women at High Risk for Breast Cancer

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: November 4, 2003
Last updated: October 27, 2012
Last verified: February 2006

RATIONALE: Screening tests such as ultrasound and mammography may help doctors detect cancer cells early and plan more effective treatment for breast cancer. It is not yet known whether ultrasound is more effective than mammography in detecting breast cancer.

PURPOSE: This clinical trial is studying breast ultrasound to see how well it works compared to mammography in detecting cancer in women who are at high risk for breast cancer.

Condition Intervention
Breast Cancer
Procedure: breast imaging study
Procedure: comparison of screening methods
Procedure: magnetic resonance imaging
Procedure: radiomammography
Procedure: ultrasound imaging

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Screening
Official Title: Screening Breast Ultrasound in High-Risk Women

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: April 2004
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:



  • Determine the diagnostic yield of whole breast bilateral screening ultrasound and mammography for the detection of breast cancer in women at high risk for breast cancer.
  • Determine the cancer detection yield of a single contrast-enhanced magnetic resonance imaging (MRI) examination after 3 rounds of annual screening with ultrasound and mammography in these participants. (MRI component of the study)


  • Determine the independent sensitivity and specificity of these screening methods in these participants.
  • Correlate performance of these screening methods with selected participant characteristics (e.g., breast density and heterogeneity of the parenchyma).
  • Validate the sonographic classification of lesions as "probably benign" and estimate the rate of malignancy in participants screened with these methods.
  • Determine the cost effectiveness associated with screening breast ultrasound, in terms of radiologist and resource time performing the exam and the induced cost of screening ultrasound (e.g., follow-up and biopsy).
  • Determine the reproducibility of lesion identification, measurement of lesion diameters, and volume and recording of lesion location on ultrasound in these participants.
  • Determine the size, type, grade, and nodal status of cancers seen only on MRI in these participants. (MRI component of the study)
  • Estimate the rate of benign biopsies and short interval follow-up induced only by MRI in these participants. (MRI component of the study)
  • Determine the cost effectiveness of MRI, including induced costs of unnecessary biopsies and follow-up. (MRI component of the study)
  • Compare the agreement among multiple examiners in sonographic, mammographic, and MRI feature analysis (using terms from the BI-RADS® lexicon) and final assessment (e.g., estimated probability of malignancy and/or recommendation for biopsy) in the enriched set of diagnostic training cases with consensus and histopathologic reference standards.

OUTLINE: This is a randomized, multicenter study. Participants are randomized to 1 of 2 screening arms.

  • Arm I: Participants undergo physician-performed bilateral whole breast ultrasound (US) followed by mammogram within 2 weeks.
  • Arm II: Participants undergo mammogram followed by physician-performed bilateral whole breast US within 2 weeks.

In both arms, participants with negative or benign findings are rescreened according to their screening arm at 1 and 2 years. Participants with "probably benign" findings are rescreened at the 6-month follow-up visit. Participants with findings that are suspicious or highly suggestive of malignancy are recommended for biopsy.

A subset of participants* in both arms undergo contrast-enhanced breast MRI within 4 weeks after completion of the 2-year screening US and mammogram. Participants with "probably benign" findings seen only on MRI may undergo an additional breast MRI at the 6-month follow-up visit. Participants with additional suspicious lesions seen only on MRI undergo second-look targeted US for biopsy guidance or MRI-guided vacuum-assisted biopsy after completion of any biopsies or additional views prompted by the 2-year screening US and mammogram visit.

NOTE: *No diagnosis of metastatic cancer of any type since entering this clinical trial.

Participants are followed annually for 3 years.

PROJECTED ACCRUAL: A total of 2,808 participants will be accrued for this study within 2 years.


Ages Eligible for Study:   25 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • At high risk for breast cancer, as defined by at least 1 of the following:

    • Known BRCA1 or BRCA2 mutation
    • Personal history of breast cancer with conserved breast analyzed separately
    • Prior biopsy showing atypical ductal hyperplasia, atypical lobular hyperplasia, or atypical papilloma and not receiving chemoprevention (i.e., not on tamoxifen, raloxifene, anastrazole, or any other aromatase inhibitor) OR any of these atypical lesions (including phyllodes tumors) AND first-degree relative diagnosed with breast cancer under age 50
    • Prior biopsy showing lobular carcinoma in situ
    • Age 30 and under and received prior chest and/or mediastinal and/or axillary irradiation ≥ 8 years ago
    • Risk of breast cancer meeting one of the following criteria:

      • Gail or Claus lifetime cancer risk ≥ 25%
      • Gail 5-year cancer risk ≥ 2.5%
      • Gail 5-year cancer risk ≥ 1.7% AND known to have extremely dense breasts (≥ 75% dense) by most recent mammogram
  • Heterogeneously dense (≥ 50% dense) or extremely dense (≥ 75% dense throughout the entire breast) breast parenchyma in at least 1 breast by mammogram* OR unknown breast density due to no prior mammogram NOTE: *No fatty breasts or minimal scattered fibroglandular density
  • Most recent mammogram* (if any) was interpreted as negative, benign, and/or remarkable only for post-treatment changes NOTE: *At least 11 full months since prior mammogram
  • No current signs or symptoms of breast cancer (e.g., palpable breast masses, bloody or spontaneous clear nipple discharge, axillary mass, or abnormal skin changes in the breast[s] or nipple[s])

    • History of breast cancer allowed provided ≥ 1 year has elapsed since the last treatment with surgery and there is no known distant metastases and no known residual tumor
  • No bilateral breast implants

    • Participants with a unilateral breast implant who would otherwise be eligible for study participation allowed (only breast without implant is evaluated)
  • Hormone receptor status:

    • Not specified



  • 25 and over


  • Female

Menopausal status

  • Not specified

Performance status

  • Not specified

Life expectancy

  • Not specified


  • Not specified


  • Not specified


  • Glomerular filtration rate ≥ 30 mL/min


  • Not pregnant or nursing
  • Fertile participants must use effective contraception
  • Able to undergo adequate mammography and cooperate with breast ultrasound
  • No concurrent medical or psychiatric condition that would preclude biopsy
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No contraindications to MRI (e.g., pacemaker, aneurysm clip, or other implanted magnetic device)*
  • No claustrophobia that cannot be controlled by medication with valium, ativan, or other sedative*
  • Must have intravenous access*
  • Weight < 300 pounds*
  • Physically able to tolerate positioning in the MRI scanner*
  • Able to undergo contrast-enhanced MRI within 4 weeks after completing both study ultrasound and mammogram at 24-month time point*
  • Agrees to undergo follow-up MRI at 6 months and/or MRI-guided vacuum-assisted biopsy or ultrasound-guided core biopsy (if needed)* NOTE: *MRI component of the study


Biologic therapy

  • Not specified


  • No concurrent chemotherapy (MRI component of the study)

Endocrine therapy

  • See Disease Characteristics
  • Concurrent chemoprevention with tamoxifen, raloxifene, anastrozole, exemestane or other aromatase inhibitor for participants with a personal history of cancer allowed (MRI component of the study)


  • See Disease Characteristics


  • See Disease Characteristics
  • More than 1 year since prior fine needle aspiration, core needle biopsy, or surgical procedure
  • No prior bilateral mastectomy (MRI component of the study)
  • More than 1 year since prior breast surgery on the study breast(s) (MRI component of the study)
  • More than 5 months since prior core biopsy of the study breast(s) (MRI component of the study)


  • More than 1 year since prior contrast-enhanced MRI of the breast
  • More than 1 year (≥ 11 full months) since prior whole breast bilateral ultrasound
  • More than 1 year since prior sonographic or mammographic contrast agent injection or tomosynthesis
  • More than 2 years since prior screening contrast-enhanced MRI of the study breast(s) (MRI component of the study)
  • More than 1 year since prior diagnostic contrast-enhanced MRI of the study breast(s) (MRI component of the study)
  • No concurrent participation in any other breast cancer screening trial
  • No concurrent participation in any other study involving breast MRI, sonographic or mammographic contrast agents, or tomosynthesis
  • No concurrent dialysis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00072501

United States, California
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
United States, Colorado
Invision - Radiology Imaging Associates
Greenwood Village, Colorado, United States, 80111
United States, Georgia
Radiology Associates of Atlanta
Atlanta, Georgia, United States, 30309
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
United States, Maryland
Johns Hopkins at Green Spring Station
Lutherville, Maryland, United States, 21093
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Ohio
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45219
Radiology Consultants, Incorporated
Youngstown, Ohio, United States, 44512
United States, Pennsylvania
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, United States, 19107-5541
Weinstein Imaging Associates
Pittsburgh, Pennsylvania, United States, 15206
Allegheny Cancer Center at Allegheny General Hospital
Pittsburgh, Pennsylvania, United States, 15212-4772
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
M.D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Centro de Estudios Radilogicos Integrales de la Mama - Buenos Aires
Buenos Aires, Argentina, 1115
Canada, Ontario
Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
American College of Radiology Imaging Network
National Cancer Institute (NCI)
Study Chair: Wendie A. Berg, MD, PhD Johns Hopkins at Green Spring Station
  More Information


Publications automatically indexed to this study by Identifier (NCT Number): Identifier: NCT00072501     History of Changes
Other Study ID Numbers: CDR0000339812
Study First Received: November 4, 2003
Last Updated: October 27, 2012

Keywords provided by National Cancer Institute (NCI):
breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases processed this record on March 29, 2017