MRI Characterization of Mammographically Detected DCIS

Study Overview
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Brief Summary
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This is a single institution, prospective observational clinical trial for women with mammographically identified calcifications that may represent ductal carcinoma in situ (DCIS). The purpose of this study is to determine whether quantitative, multiparametric breast MRI performed prior to surgical resection can biologically characterize this common pre-invasive malignancy, ductal carcinoma in situ (DCIS), which typically presents in asymptomatic women as suspicious calcifications on mammography.

Detailed Description
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The investigators will assess whether MRI signatures can determine which calcifications identified prior to surgical resection actually harbor DCIS, and whether these imaging features correlate with pathologic markers of proliferation (Ki-67) and inflammation (cox-2) within DCIS lesions. The investigators will also explore whether quantitative MRI features in the peri-tumoral region correlate with prognostic microenvironment markers of inflammation (TNFα) and angiogenesis (VEGF). Finally, investigators will assess whether a multivariate model using these markers can accurately predict risk of recurrence based on a multi-gene assay (Oncotype DX DCIS score).

Official Title
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MRI Characterization of Mammographically Detected Calcifications and Ductal Carcinoma in Situ

Conditions
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Breast Cancer, Stage 0

Intervention / Treatment
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* Diagnostic Test: Breast MRI
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: [Cohort A] Women aged 18 or older with suspicious calcifications identified on mammography without an associated mass [Cohort B] Women aged 18 or older with recent biopsy-proven DCIS with residual calcifications present on mammogram after biopsy Exclusion Criteria for Both Cohorts: Patients with prior history of breast cancer in the ipsilateral breast Patients with a newly diagnosed breast cancer in the contralateral breast Contra-indication to contrast-enhanced breast MRI (e.g. renal insufficiency with GFR<60, contrast allergy, incompatible metal) Patients who currently are undergoing chemoprevention therapy (e.g. aromatase inhibitors or selective estrogen receptor modulators) Women who are pregnant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort A<br>Patient with recently identified calcifications on mammography requiring biopsy. Patients will undergo a quantitative, multiparametric breast MRI as part of their clinical care. MRI will not change need for biopsy, but could identify additional suspicious sites. Only patients diagnosed with pure DCIS at biopsy and eventual surgical excision will receive Oncotype DX DCIS score testing. | Diagnostic Test: Breast MRI<br>* Quantitative, multiparametric breast MRI<br>Other: Laboratory Biomarker Analysis<br>* Only patients with pure DCIS on surgical excision will have advanced pathologic markers and Oncotype Dx DCIS Score testing.<br>* Other names: Oncotype Dx;|
| Cohort B<br>Patient with recent diagnosis of biopsy-proven DCIS would complete a research quantitative, multiparametric breast MRI as part of their clinical care. Only patients diagnosed with pure DCIS at surgical resection will receive Oncotype DX DCIS score testing. | Diagnostic Test: Breast MRI<br>* Quantitative, multiparametric breast MRI<br>Other: Laboratory Biomarker Analysis<br>* Only patients with pure DCIS on surgical excision will have advanced pathologic markers and Oncotype Dx DCIS Score testing.<br>* Other names: Oncotype Dx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional perfusion (f) | Assess whether high f within DCIS lesions correlates with proliferation (high Ki-67) | 3.5 years | 
| Tissue diffusion (Dt) | Assess whether low Dt within DCIS lesions correlates with high proliferation (Ki-67) | 3.5 years | 
| Transfer constant (Ktrans) | Assess whether high Ktrans within DCIS lesions correlates with inflammation (cox-2) | 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Signal enhancement ratio (SER) | Assess whether low SER can exclude the presence of DCIS-associated malignancy at the site of mammographic calcifications | 3.5 years | 
| Apparent diffusion coefficient (ADC) | Assess whether high ADC can exclude the presence of DCIS-associated malignancy at the site of mammographic calcifications | 3.5 years | 
| Oncotype DCIS Score | Develop a multivariate MRI model to identify low risk DCIS (Oncotype DX DCIS score<39) | 3.5 years | 
| Transfer constant (Ktrans) | Assess whether high Ktrans in the peri-tumoral tissue correlates with stromal inflammation (TNFalpha) | 3.5 years | 
| Fractional perfusion (f) | Assess whether high f in the peri-tumoral tissue correlates with angiogenesis (VEGF) | 3.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ductal Carcinoma in Situ, MRI, Oncotype Dx