Combined Breast MRI and Biomarker Strategies in Identifying High-risk Breast Cancer Patients

Study Overview
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Brief Summary
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This clinical trial studies normal breast tissue changes combined with breast magnetic resonance imaging (MRI) that may suggest the beginnings of cancer development. Using breast tissue markers in combination with breast imaging such as MRI may help to more accurately assess a woman's risk of developing breast cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the number of high risk women with abnormal screening breast MRI and morphologically normal biopsy over 7 years. SECONDARY OBJECTIVES: I. To determine if WNT10B/mutant p53 expression as measured in the 0-month biopsy predicts women with an abnormal MRI/non-cancerous biopsy who will progress to cancer over 7 years. TERTIARY OBJECTIVES: I. To determine the predictive accuracy of WNT10B with MRI, of which will be compared with MRI alone using the C-index. OUTLINE: Participants undergo standard of care high risk breast cancer screening MRIs at baseline and follow-up and blood sample collection at baseline. Participants undergo collection of breast tissue samples at any breast biopsy or breast surgery.

Official Title
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Combined Breast MRI/Biomarker Strategies to Identify Aggressive Biology

Conditions
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Healthy Subject

Intervention / Treatment
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* Procedure: Magnetic Resonance Imaging
* Procedure: Biospecimen Collection
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women who are undergoing screening breast MRI as per standard of care for high-risk breast cancer screening Willing to donate left-over tissue if patient undergoes a breast biopsy and/or breast surgery Willing to have about 40 mL of blood (approximately 3 tablespoons) drawn Documented informed consent of the participant Exclusion Criteria: Allergy or intolerance to gadolinium Inability to undergo breast MRI (e.g. claustrophobia) Participants with active cancer diagnosis (exception: skin cancer, biopsy-proven atypical lobular, ductal hyperplasia and/or lobular carcinoma in situ) Previous diagnosis of stage 4 cancer Participants who have received cytotoxic chemotherapy within 1 year prior to screening breast MRI Participants who have received endocrine therapy within 1 year prior to screening breast MRI Participants who have received breast radiation within 1 year prior to screening breast MRI Radiation to both breasts Pregnant and/or lactating within 1 year prior to screening breast MRI Receives screening breast MRIs at an outside facility other than the consenting institution

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (breast MRI, biopsy)<br>Participants undergo standard of care high risk breast cancer screening MRIs at baseline and follow-up and blood sample collection at baseline. Participants also undergo collection of breast tissue samples at any breast biopsy or breast surgery. | Procedure: Magnetic Resonance Imaging<br>* Undergo high risk breast cancer screening MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Procedure: Biospecimen Collection<br>* Undergo blood and tissue sample collection<br>Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of triple-negative breast cancer (invasive and/or ductal carcinoma in situ [DCIS]) within the 12-month period of the study | Development of breast cancers other than triple-negative (e.g. estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) the study analysis, however they will be reported as descriptive statistics. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of WNT10B/mutant p53 in morphologically normal breast tissue | Biopsy tissue will be assessed for 1) activated WNT10B (measured by presence of high phospho-beta-catenin; present vs. absent) and 2) loss of p53 function (measured by the loss of p21 expression; present versus [vs.] absent). The optimal cut for the WNT10B to differentiate progression vs. non-progression women will be carried out by receiver operating characteristic (ROC) analysis, and hence WNT10B expression will be dichotomized to high vs. low expression. Chi-square test 12-month progression. Adjusted association will be further explored by logistic regression incorporating subject characteristics, such as age, body mass index (BMI), race, and BRCA1. | Up to 12 months |