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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Asymptomatic

Intervention / Treatment
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* Diagnostic Test: Contrast-enhanced Magnetic Resonance Imaging
* Diagnostic Test: Digital Tomosynthesis Mammography
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (DBT, AB-MR)<br>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. | Diagnostic Test: Contrast-enhanced Magnetic Resonance Imaging<br>* Undergo AB-MR<br>* Other names: Contrast-enhanced MRI;Diagnostic Test: Digital Tomosynthesis Mammography<br>* Undergo DBT<br>* Other names: Digital Tomosynthesis of the Breast;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm B (AB-MR, DBT)<br>Participants undergo AB-MR for under 10 minutes followed by DBT on the same day or within 24 hours at baseline and then after 1year. | Diagnostic Test: Contrast-enhanced Magnetic Resonance Imaging<br>* Undergo AB-MR<br>* Other names: Contrast-enhanced MRI;Diagnostic Test: Digital Tomosynthesis Mammography<br>* Undergo DBT<br>* Other names: Digital Tomosynthesis of the Breast;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Ductal Carcinoma in Situ (DCIS) Detected on Abbreviated Breast-magnetic Resonance (MR) and Digital Tomosynthesis Mammography (DBT) | Descriptive Analyses presenting the the distributions of Oncotype-DCIS scores by modality 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 | 
| Incident Cancer Rate | Breast cancer incidence will be estimated. Person-years will be measured. | Up to 3 years | 
| 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. | end of study |