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

NCT ID: NCT00072501

Last Updated: 2012-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2004-04-30

Brief Summary

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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.

Detailed Description

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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

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Breast Cancer

Keywords

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breast cancer

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

SCREENING

Interventions

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breast imaging study

Intervention Type PROCEDURE

comparison of screening methods

Intervention Type PROCEDURE

magnetic resonance imaging

Intervention Type PROCEDURE

radiomammography

Intervention Type PROCEDURE

ultrasound imaging

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

25 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

American College of Radiology Imaging Network

NETWORK

Sponsor Role lead

Principal Investigators

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Wendie A. Berg, MD, PhD

Role: STUDY_CHAIR

Johns Hopkins at Green Spring Station

Locations

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USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, United States

Site Status

Invision - Radiology Imaging Associates

Greenwood Village, Colorado, United States

Site Status

Radiology Associates of Atlanta

Atlanta, Georgia, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Site Status

Johns Hopkins at Green Spring Station

Lutherville, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

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

Chapel Hill, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Site Status

Radiology Consultants, Incorporated

Youngstown, Ohio, United States

Site Status

Kimmel Cancer Center at Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Weinstein Imaging Associates

Pittsburgh, Pennsylvania, United States

Site Status

Allegheny Cancer Center at Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

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

Dallas, Texas, United States

Site Status

M.D. Anderson Cancer Center at University of Texas

Houston, Texas, United States

Site Status

Centro de Estudios Radilogicos Integrales de la Mama - Buenos Aires

Buenos Aires, , Argentina

Site Status

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

Toronto, Ontario, Canada

Site Status

Countries

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United States Argentina Canada

References

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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.

Reference Type BACKGROUND
PMID: 16641344 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16641345 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15337420 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12704027 (View on PubMed)

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.

Reference Type RESULT
PMID: 22733916 (View on PubMed)

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.

Reference Type RESULT
PMID: 22474203 (View on PubMed)

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.

Reference Type RESULT
PMID: 20032143 (View on PubMed)

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.

Reference Type RESULT
PMID: 20868895 (View on PubMed)

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.

Reference Type RESULT
PMID: 18477782 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26712110 (View on PubMed)

Other Identifiers

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ACRIN-6666

Identifier Type: -

Identifier Source: secondary_id

CDR0000339812

Identifier Type: -

Identifier Source: org_study_id