Abbreviated Breast MRI and Digital Tomosynthesis Mammography in Screening Women With Dense Breasts

Asymptomatic Clinical Trial

Official title:

Comparison of Abbreviated Breast MRI and Digital Breast Tomosynthesis in Breast Cancer Screening in Women With Dense Breasts

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02933489
• Other study ID #: EA1141
• Secondary ID: NCI-2016-00252s1
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 27, 2016
• Est. completion date: January 31, 2025

Study information

• Verified date: May 2024
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well abbreviated breast magnetic resonance imaging (MRI) and digital tomosynthesis mammography work in detecting cancer in women with dense breasts. Abbreviated breast MRI is a low cost procedure in which radio waves and a powerful magnet linked to a computer and used to create detailed pictures of the breast in less than 10 minutes. These pictures can show the difference between normal and diseased tissue. Digital tomosynthesis mammography is a procedure that uses multiple x-rays pictures of each breast to produce a 3-dimensional rendering of the entire breast. Combined screening with abbreviated breast MRI and digital tomosynthesis mammography may be a better method to screen women with dense breasts.

Description:

PRIMARY OBJECTIVES:

I. To compare the rates of detection of invasive cancers between the initial abbreviated breast (AB)-magnetic resonance (MR) and digital tomosynthesis mammography (DBT).

SECONDARY OBJECTIVES:

I. To compare the positive predictive value (PPV) of biopsies, call back rates, and short-term follow up rates after AB-MR and DBT on both the initial and 1 year follow up studies.

II. To estimate and compare the sensitivity and specificity of AB-MR and DBT, using the 1 year follow up to define a reference standard.

III. To compare patient-reported short-term quality of life related to diagnostic testing with AB-MR and DBT using the Testing Morbidities Index.

IV. To compare willingness to return for testing with AB-MRI versus (vs) DBT within the recommended screening interval and explore factors associated with willingness to return for screening.

V. To compare the tumor biologies of invasive cancers and ductal carcinoma in situ (DCIS) detected on AB-MR and DBT.

VI. To estimate the incident cancer rate during 3 years following the year-1 AB-MR/DBT when patients return to standard screening.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM A (DBT, AB-MR): Participants undergo DBT followed by AB-MR for under 10 minutes on the same day or within 24 hours at baseline and then after 1 year.

ARM B (AB-MR, DBT): Participants undergo AB-MR for under 10 minutes followed by DBT on the same day or within 24 hours at baseline and then after 1 year.

After completion of study, patients are followed up at every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1516
• Est. completion date: January 31, 2025
• Est. primary completion date: January 23, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 40 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patents must be scheduled for routine screening DBT

• Women must not be pregnant or breast-feeding; all females of childbearing potential who are uncertain if they could be pregnant or may be pregnant or as per local site standard of practice in women undergoing DBT and MRI must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy; a female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)

• Women of childbearing potential must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the following year until the year 1 AB-MR and DBT studies are performed

• Patient?s breast density must be known; patients must have mammographically dense breasts, American College of Radiology [ACR] Breast Imaging [BI]- Reporting and Data System Atlas (RADS) lexicon categories c or d (heterogeneous or extreme fibroglandular tissue) on their most-recent prior screening

• Patient must be asymptomatic for breast disease and undergoing routine screening

• Patient must have no known breast cancer (DCIS or invasive cancer), not currently undergoing treatment for breast cancer, or planning surgery for a high risk lesion (atypical ductal breast hyperplasia [ADH], atypical lobular breast hyperplasia [ALH], lobular breast carcinoma in situ [LCIS], papilloma, radial scar)

• Patient must not be taking chemoprevention for breast cancer

• Patient must not have undergone breast ultrasound within 12 months prior to randomization

• Patient must not have previously had a breast MRI

• Patient must not have previously had molecular breast imaging (MBI, multiplexed ion beam imaging [MIBI])

• Patient must agree to not undergo screening ultrasound (of breast) for the duration of the 1 year study period

• Patient must not be suspected of being at high-risk for breast cancer, as defined by the American Cancer Society (ACS) breast MR screening recommendations (lifetime risk of >= 20-25%)

• Patient must be able to undergo breast MRI with contrast enhancement; patients unable to undergo breast MRI with contrast enhancement for any reason are ineligible

• No history of untreatable claustrophobia

• No presence of non MR compatible metallic objects or metallic objects that, in the opinion of the radiologist, would make MRI a contraindication

• No history of sickle cell disease

• No contraindication to intravenous contrast administration

• No known allergy-like reaction to gadolinium or moderate or severe allergic reactions to one or more allergens as defined by the American College of Radiology (ACR); patient may be eligible if willing to undergo pre-treatment as defined by the institution's policy and/or ACR guidance

• No known or suspected renal impairment; requirements for glomerular filtration rate (GFR) prior to MRI as determined by local site standard practice

• Weight less than or equal to the MRI table limit

• No women who have had prior contrast enhanced mammography (contrast enhanced spectral mammography [CESM] or contrast enhanced digital mammography [CEDM])

• No women who have breast prosthetic implants (silicone or saline) Exclusion Criteria

Related Conditions & MeSH terms

• Asymptomatic

Intervention

Diagnostic Test:
• Contrast-enhanced Magnetic Resonance Imaging
Undergo AB-MR
• Digital Tomosynthesis Mammography
Undergo DBT

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
Germany	Rwth Klinikum Aachen	Aachen
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Aultman Health Foundation	Canton	Ohio
United States	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Sentara Martha Jefferson Hospital	Charlottesville	Virginia
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	Northwestern University	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	Case Western Reserve University	Cleveland	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	The Women's Imaging Center	Denver	Colorado
United States	Essentia Health Cancer Center	Duluth	Minnesota
United States	Radiology Imaging Associates	Englewood	Colorado
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Farmington Health Center	Farmington	Utah
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Mercy Health Saint Mary's	Grand Rapids	Michigan
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Diagnostic Center for Women LLC	Miami	Florida
United States	ProHealth D N Greenwald Center	Mukwonago	Wisconsin
United States	The Community Hospital	Munster	Indiana
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Sentara Leigh Hospital	Norfolk	Virginia
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Norwalk Hospital	Norwalk	Connecticut
United States	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Huntington Memorial Hospital	Pasadena	California
United States	ECOG-ACRIN Cancer Research Group	Philadelphia	Pennsylvania
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Riverview Medical Center/Booker Cancer Center	Red Bank	New Jersey
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	South Jordan Health Center	South Jordan	Utah
United States	Spartanburg Medical Center	Spartanburg	South Carolina
United States	Clinical Radiologists SC	Springfield	Illinois
United States	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
ECOG-ACRIN Cancer Research Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Germany, 

References & Publications (1)

Comstock CE, Gatsonis C, Newstead GM, Snyder BS, Gareen IF, Bergin JT, Rahbar H, Sung JS, Jacobs C, Harvey JA, Nicholson MH, Ward RC, Holt J, Prather A, Miller KD, Schnall MD, Kuhl CK. Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis f — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Screen-detected Invasive Cancer Verified by Pathology	For each modality, the detection rate of invasive cancers is defined as the proportion of participants who had an invasive cancer detected by the modality at baseline and verified by pathology versus the total number of participants. In the out come measures table below, these proportions will be automatically calculated, multiplied by 100, and be presented as percentages (%).	Up to 1 year
Secondary	Positive Predictive Value (PPV) of Biopsies	Test Positive (T+): Biopsy recommended by imaging, defined as patients with at least one lesion rated BI-RADS 4 or 5 on image interpretation. Reference Standard Positive (RS+): Pathologically confirmed DCIS or invasive disease resultant from a positive test.; The 95% confidence interval for PPV of biopsy for each modality were derived from the GEE model using the appropriate estimable contrasts with robust standard errors	Baseline to up to 1 year
Secondary	Call Back/Additional Imaging/Short-term Follow Rates for DBT and AB-MR	For DBT: DBT: Call back is defined as having additional views or targeted ultrasound to evaluate DBT findings DBT: short term follow up (STFU) is defined as having at least one lesion rated BI-RADS 3 on DBT DBT: Additional imaging recommendation is defined as having either call back or STFU; For AB-MR: Ab-MR: Call back does not apply to AB-MR and will not be evaluated Ab-MR: Short Term Follow-up (STFU) is defined as having at least one lesion rated BI-RADS 3 on AB-MR Ab-MR: Additional imaging recommendation is defined as having a STFU	Baseline
Secondary	Prediction of Breast Cancer (Sensitivity and Specificity)	Reference standard positive (RS+): breast cancer (invasive or DCIS) detected on the year 0 screening or reported at any time from the year 0 to the year 1 screening.; Reference standard negative (RS-): No breast cancer reported at any time from the year 0 to the year 1 screen.; Incomplete: No Year 1 imaging, and <11 months of patient follow-up (<330 days) after year 0 screen; Positive Test (T+) is defined as the imaging modality result is positive (BI-RADS 3-5), and the location of the finding is matches the location of the cancer indicated by the reference standard.; Negative Test (T-) will be estimated as the fraction of reference standard negative subjects for whom the imaging modality result was negative (BI-RADS 1-2).; 95% confidence intervals for the sensitivity and specificity of each modality calculated using the Wilson method.	Baseline to up to 1 year
Secondary	Change in Patient-reported Short-term Quality of Life Related to Diagnostic Testing	Testing Morbidities Index (TMI) scores [0 (worst) to 100 (best) scale] will be computed for abbreviated breast-magnetic resonance (MR) and digital tomosynthesis mammography (DBT) after the baseline screen.	Baseline to up to 1 year
Secondary	Willingness to Return for Testing With Abbreviated Breast-magnetic Resonance (MR) Versus Digital Tomosynthesis Mammography (DBT)	The proportions of participants willing to return for screening with either test, AB-MRI only, DBT only, or not willing to return for either test will be estimated.	Up to 1 year
Secondary	Factors Associated With Willingness to Return for Screening	Polytomous logistic regression will be used to examine factors associated with willingness to return, including screen result, cancer status, and demographic characteristics.	Up to 1 year
Secondary	Oncotype-DCIS Scores by Modality	Descriptive Analyses presenting the the distributions of Oncotype-DCIS scores by modality: Ductal carcinoma in situ (DCIS) detected on abbreviated breast-magnetic resonance (MR) and digital tomosynthesis mammography (DBT) A low risk score is less than 39, and a high risk score is 55 or higher. A score of 39 to 54 is intermediate risk.	Up to 1 year
Secondary	Incident Cancer Rate	Breast cancer incidence will be estimated. Person-years will be measured.	Up to 3 years
Secondary	NanoString Tumor Biologies of Invasive Cancers and Ductal Carcinoma in Situ (DCIS) Detected on AB-MR and DBT	For all invasive cancers detected during the study period, the NanoString PAM50 will be performed. The frequencies of cancer types determined by the NanoString analysis will be tabulated and compared. For DCIS, if the Oncotype-DCIS score was performed, the distributions of scores will be tabulated and compared.; All efforts to obtain NanoString data have been exhausted, therefore we have no data available to report.	end of study

External Links

•   Primary Manuscript