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Breast CancerNCT00072501

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

A study testing breast imaging study, comparison of screening methods and magnetic resonance imaging in people with Breast Cancer, run by American College of Radiology Imaging Network at 20 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 25 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
breast imaging study, comparison of screening methods and magnetic resonance imaging
Type of treatment
Surgery or procedure
How many people
Not given
Where
20 sitesin 3 countries
Study dates
Apr 2004to Apr 2012
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

Age

  • 25 and over

Sex

  • Female

Menopausal status

  • Not specified

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Glomerular filtration rate ≥ 30 mL/min

Other

  • 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • 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)

Radiotherapy

  • See Disease Characteristics

Surgery

  • 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)

Other

  • 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

Trial locations and contacts

20 sites in 3 countries.

20 sites in 3 countries

United States18 sites

  • Radiology Associates of Atlanta

    Atlanta, Georgia, 30309

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

    Chapel Hill, North Carolina, 27599-7295

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • Charles M. Barrett Cancer Center at University Hospital

    Cincinnati, Ohio, 45219

  • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

    Dallas, Texas, 75390

  • Duke Comprehensive Cancer Center

    Durham, North Carolina, 27710

  • Invision - Radiology Imaging Associates

    Greenwood Village, Colorado, 80111

  • M.D. Anderson Cancer Center at University of Texas

    Houston, Texas, 77030-4009

  • USC/Norris Comprehensive Cancer Center and Hospital

    Los Angeles, California, 90089-9181

  • Jonsson Comprehensive Cancer Center at UCLA

    Los Angeles, California, 90095-1781

  • Johns Hopkins at Green Spring Station

    Lutherville, Maryland, 21093

  • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

    Philadelphia, Pennsylvania, 19107-5541

  • Weinstein Imaging Associates

    Pittsburgh, Pennsylvania, 15206

  • Allegheny Cancer Center at Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212-4772

  • Mayo Clinic Cancer Center

    Rochester, Minnesota, 55905

  • Siteman Cancer Center at Barnes-Jewish Hospital

    St Louis, Missouri, 63110

  • Radiology Consultants, Incorporated

    Youngstown, Ohio, 44512

Other trials in United States

Argentina1 site

  • Centro de Estudios Radilogicos Integrales de la Mama - Buenos Aires

    Buenos Aires, 1115

Other trials in Argentina

Canada1 site

  • Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: 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.

Read the detailed description

OBJECTIVES:

Primary

  • 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)

Secondary

  • 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.

Conditions
Breast Cancer
Being tested
breast imaging study, comparison of screening methods, magnetic resonance imaging, radiomammography, ultrasound imaging
Keywords
breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • breast imaging studyProcedure or surgery

  • comparison of screening methodsProcedure or surgery

  • magnetic resonance imagingProcedure or surgery

  • radiomammographyProcedure or surgery

  • ultrasound imagingProcedure or surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Nov 2003 (estimated)
  2. Study startApr 2004
  3. Primary completionApr 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Screening
Allocation
Randomised
IDs, dates and publications
ClinicalTrials.gov ID
NCT00072501
Sponsor's protocol ID
CDR0000339812
Other IDs
ACRIN-6666
Status last verified
Feb 2006
First submitted
4 Nov 2003
Last updated
30 Oct 2012
Results posted
No

Publications

  • Berg WA, Blume JD, Cormack JB, Mendelson EB, Madsen EL; ACRIN 6666 Investigators. Lesion detection and characterization in a breast US phantom: results of the ACRIN 6666 Investigators. Radiology. 2006 Jun;239(3):693-702. doi: 10.1148/radiol.2393051069. Epub 2006 Apr 26.

    PubMed 16641344

  • Madsen EL, Berg WA, Mendelson EB, Frank GR; Investigators for ACRIN Protocol 6666. Anthropomorphic breast phantoms for qualification of Investigators for ACRIN Protocol 6666. Radiology. 2006 Jun;239(3):869-74. doi: 10.1148/radiol.2393051070. Epub 2006 Apr 26.

    PubMed 16641345

  • Berg WA. Supplemental screening sonography in dense breasts. Radiol Clin North Am. 2004 Sep;42(5):845-51, vi. doi: 10.1016/j.rcl.2004.04.003.

    PubMed 15337420

  • Berg WA. Rationale for a trial of screening breast ultrasound: American College of Radiology Imaging Network (ACRIN) 6666. AJR Am J Roentgenol. 2003 May;180(5):1225-8. doi: 10.2214/ajr.180.5.1801225. No abstract available.

    PubMed 12704027

  • Berg WA, Blume JD, Cormack JB, Mendelson EB. Training the ACRIN 6666 Investigators and effects of feedback on breast ultrasound interpretive performance and agreement in BI-RADS ultrasound feature analysis. AJR Am J Roentgenol. 2012 Jul;199(1):224-35. doi: 10.2214/AJR.11.7324.

    PubMed 22733916

  • Berg WA, Zhang Z, Lehrer D, Jong RA, Pisano ED, Barr RG, Bohm-Velez M, Mahoney MC, Evans WP 3rd, Larsen LH, Morton MJ, Mendelson EB, Farria DM, Cormack JB, Marques HS, Adams A, Yeh NM, Gabrielli G; ACRIN 6666 Investigators. Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. JAMA. 2012 Apr 4;307(13):1394-404. doi: 10.1001/jama.2012.388.

    PubMed 22474203

  • Berg WA, Blume JD, Adams AM, Jong RA, Barr RG, Lehrer DE, Pisano ED, Evans WP 3rd, Mahoney MC, Hovanessian Larsen L, Gabrielli GJ, Mendelson EB. Reasons women at elevated risk of breast cancer refuse breast MR imaging screening: ACRIN 6666. Radiology. 2010 Jan;254(1):79-87. doi: 10.1148/radiol.2541090953.

    PubMed 20032143

  • Berg WA, Sechtin AG, Marques H, Zhang Z. Cystic breast masses and the ACRIN 6666 experience. Radiol Clin North Am. 2010 Sep;48(5):931-87. doi: 10.1016/j.rcl.2010.06.007.

    PubMed 20868895

  • Berg WA, Blume JD, Cormack JB, Mendelson EB, Lehrer D, Bohm-Velez M, Pisano ED, Jong RA, Evans WP, Morton MJ, Mahoney MC, Larsen LH, Barr RG, Farria DM, Marques HS, Boparai K; ACRIN 6666 Investigators. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA. 2008 May 14;299(18):2151-63. doi: 10.1001/jama.299.18.2151.

    PubMed 18477782

  • Berg WA, Bandos AI, Mendelson EB, Lehrer D, Jong RA, Pisano ED. Ultrasound as the Primary Screening Test for Breast Cancer: Analysis From ACRIN 6666. J Natl Cancer Inst. 2015 Dec 28;108(4):djv367. doi: 10.1093/jnci/djv367. Print 2016 Apr.

    PubMed 26712110

Questions about this trial

What is this clinical trial studying?

A study testing breast imaging study, comparison of screening methods and magnetic resonance imaging in people with Breast Cancer, run by American College of Radiology Imaging Network at 20 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, Argentina, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00072501, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2012.

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