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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00072501
Recruitment Status : Completed
First Posted : November 6, 2003
Last Update Posted : October 30, 2012
National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)

November 4, 2003
November 6, 2003
October 30, 2012
April 2004
April 2012   (Final data collection date for primary outcome measure)
Not Provided
Not Provided
Complete list of historical versions of study NCT00072501 on Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
Breast Ultrasound and Mammography in Screening Women at High Risk for Breast Cancer
Screening Breast Ultrasound in High-Risk Women

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.



  • 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.

Not Applicable
Allocation: Randomized
Primary Purpose: Screening
Breast Cancer
  • Procedure: breast imaging study
  • Procedure: comparison of screening methods
  • Procedure: magnetic resonance imaging
  • Procedure: radiomammography
  • Procedure: ultrasound imaging
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Not Provided
Not Provided
Not Provided
April 2012   (Final data collection date for primary outcome measure)


  • 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
Sexes Eligible for Study: Female
25 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Argentina,   Canada,   United States
Not Provided
Not Provided
Not Provided
Not Provided
American College of Radiology Imaging Network
National Cancer Institute (NCI)
Study Chair: Wendie A. Berg, MD, PhD Johns Hopkins at Green Spring Station
National Cancer Institute (NCI)
February 2006

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP