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

Breast Cancer Clinical Trial

Official title:

Screening Breast Ultrasound in High-Risk Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00072501
• Other study ID #: CDR0000339812
• Secondary ID: ACRIN-6666
• Status: Completed
• Phase: N/A
• First received: November 4, 2003
• Last updated: October 27, 2012
• Start date: April 2004

Study information

• Verified date: February 2006
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Screening

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• breast imaging study

• comparison of screening methods

• magnetic resonance imaging

• radiomammography

• ultrasound imaging

Locations

Country	Name	City	State
Argentina	Centro de Estudios Radilogicos Integrales de la Mama - Buenos Aires	Buenos Aires
Canada	Toronto Sunnybrook Regional Cancer Centre at Sunnybrook and Women's College Health Sciences Centre	Toronto	Ontario
United States	Radiology Associates of Atlanta	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Invision - Radiology Imaging Associates	Greenwood Village	Colorado
United States	M.D. Anderson Cancer Center at University of Texas	Houston	Texas
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Johns Hopkins at Green Spring Station	Lutherville	Maryland
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	Weinstein Imaging Associates	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Radiology Consultants, Incorporated	Youngstown	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
American College of Radiology Imaging Network	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Argentina,  Canada, 

References & Publications (9)

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. 201 — View Citation

Berg WA, Blume JD, Cormack JB, Mendelson EB, Lehrer D, Böhm-Vélez 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 — View Citation

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. Epub 2006 Apr 26. — View Citation

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 — View Citation

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. Review. — View Citation

Berg WA, Zhang Z, Lehrer D, Jong RA, Pisano ED, Barr RG, Böhm-Vélez 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 — View Citation

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. Review. — View Citation

Berg WA. Supplemental screening sonography in dense breasts. Radiol Clin North Am. 2004 Sep;42(5):845-51, vi. Review. — View Citation

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. Epub 2006 Apr 26. — View Citation