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

• ClinicalTrials.gov Identifier: NCT03303846
• Recruitment Status: Recruiting
• First Posted: October 6, 2017
• Last Update Posted: November 25, 2022
• Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): City of Hope Medical Center

Tracking Information

• First Submitted Date: October 3, 2017
• First Posted Date: October 6, 2017
• Last Update Posted Date: November 25, 2022
• Actual Study Start Date: October 13, 2017
• Estimated Primary Completion Date: October 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2017)

Incidence of triple-negative breast cancer (invasive and/or ductal carcinoma in situ [DCIS]) within the 12-month period of the study [ Time Frame: Up to 12 months ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 3, 2017)

Expression of WNT10B/mutant p53 in morphologically normal breast tissue [ Time Frame: Up to 12 months ]

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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: October 3, 2017)

Predictive accuracy of WNT10B with magnetic resonance imaging (MRI) [ Time Frame: Up to 12 months ]

The specificity for MRI combined with WNT10B and/or p53 based biomarkers to detect triple negative breast cancer (TNBC) will be calculated with 95% confidence interval (CI). Its prediction accuracy will be described by C-index and compared to that by diagnosis by MRI alone.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Combined Breast MRI and Biomarker Strategies in Identifying High-risk Breast Cancer Patients
• Official Title: Combined Breast MRI/Biomarker Strategies to Identify Aggressive Biology
• Brief Summary: 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

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.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Screening
• Condition: Healthy Subject

Intervention

• Procedure: Magnetic Resonance Imaging
  Undergo high risk breast cancer screening MRI
  Other Names:

  • Magnetic Resonance / Nuclear Magnetic Resonance
  • MRI
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
• Procedure: Biospecimen Collection
  Undergo blood and tissue sample collection
• Other: Laboratory Biomarker Analysis
  Correlative studies

Study Arms

Experimental: Treatment (breast MRI, biopsy)

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.

Interventions:

• Procedure: Magnetic Resonance Imaging
• Procedure: Biospecimen Collection
• Other: Laboratory Biomarker Analysis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 3, 2017): 650
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2023
• Estimated Primary Completion Date: October 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03303846
• Other Study ID Numbers: 17009; NCI-2017-01757 ( Registry Identifier: NCI CTRP ); U01CA189283 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: City of Hope Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: City of Hope Medical Center
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Victoria Seewaldt, MD; City of Hope Medical Center

• PRS Account: City of Hope Medical Center
• Verification Date: November 2022