MRI Characterization of Mammographically Detected DCIS

MRI Characterization of Mammographically Detected Calcifications and Ductal Carcinoma in Situ

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer, Stage 0
• Intervention / Treatment: Diagnostic test: Breast MRI; Other: Laboratory Biomarker Analysis

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 122

Contacts and Locations

• Study Contact: Name: Habib Rahbar; Phone Number: 206-606-6777; Email: b-imaging-research@seattlecca.org
• Study Contact Backup: Name: Mary Lynn Bryant; Phone Number: 937-540-0802; Email: b-imaging-research@seattlecca.org

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Women aged 18 or older with suspicious mammographic caclifications or biopsy-proven DCIS with residual calcifications present on mammogram after biopsy. Study participants will undergo an experimental 3 Tesla breast MRI prior to surgical resection, including both DWI and DCE techniques. Only participants who are diagnosed with pure DCIS on both core needle biopsy and surgical resection will remain on study. Tissue from all DCIS lesions will also be sent for outside multi-gene assay testing (Oncotype DX DCIS score, Genomic Health, Redwood City, CA).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort A; 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; Quantitative, multiparametric breast MRI; Other: Laboratory Biomarker Analysis; Only patients with pure DCIS on surgical excision will have advanced pathologic markers and Oncotype Dx DCIS Score testing.; Other Names: Oncotype Dx
Cohort B; 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; Quantitative, multiparametric breast MRI; Other: Laboratory Biomarker Analysis; Only patients with pure DCIS on surgical excision will have advanced pathologic markers and Oncotype Dx DCIS Score testing.; Other Names: Oncotype Dx

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Habib Rahbar, Fred Hutch/University of Washington Cancer Consortium

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2018
• Primary Completion (Actual): April 30, 2023
• Study Completion (Estimated): April 1, 2032

Study Registration Dates

• First Submitted: April 4, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (Actual): April 11, 2018

Study Record Updates

• Last Update Posted (Actual): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Ductal Carcinoma in Situ; Oncotype Dx
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Breast Diseases; Breast Neoplasms; Carcinoma in Situ; Breast Carcinoma In Situ
• Other Study ID Numbers: 9778; R01CA203883 (U.S. NIH Grant/Contract); RG3017004 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); NCI-2021-12034 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No