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Screening Breast Ultrasound in High-Risk Women

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Breast Cancer

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Trial Information

Screening Breast Ultrasound in High-Risk Women



- 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

- 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

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

Inclusion Criteria


- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Screening

Principal Investigator

Wendie A. Berg, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Johns Hopkins at Green Spring Station


United States: Federal Government

Study ID:




Start Date:

April 2004

Completion Date:

Related Keywords:

  • Breast Cancer
  • breast cancer
  • Breast Neoplasms



Mayo Clinic Cancer Center Rochester, Minnesota  55905
Duke Comprehensive Cancer Center Durham, North Carolina  27710
Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Siteman Cancer Center at Barnes-Jewish Hospital Saint Louis, Missouri  63110
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill Chapel Hill, North Carolina  27599-7570
Charles M. Barrett Cancer Center at University Hospital Cincinnati, Ohio  45267-0526
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
USC/Norris Comprehensive Cancer Center and Hospital Los Angeles, California  90033-0804
M.D. Anderson Cancer Center at University of Texas Houston, Texas  77030
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Allegheny Cancer Center at Allegheny General Hospital Pittsburgh, Pennsylvania  15212
Radiology Consultants, Incorporated Youngstown, Ohio  44512
Invision - Radiology Imaging Associates Greenwood Village, Colorado  80111
Radiology Associates of Atlanta Atlanta, Georgia  30309
Johns Hopkins at Green Spring Station Lutherville, Maryland  21093
Weinstein Imaging Associates Pittsburgh, Pennsylvania  15206