Early Detection of Breast Cancer in Women With Suspicious Mammograms

This is a non-treatment study. It will not involve the use of any investigational drug or device. Potential participants will be enrolled through direct contact with collaborating clinical sites when the patient's annual 3D mammogram report yields a BIRADS rating of 4-5. The clinical Investigators or a member of their staff will conduct consent discussion once a suspicious mammogram report is identified or if a patient is referred for imaging of a suspicious area in the breast. After consenting the participant will be asked to donate a blood sample, a saliva sample, medical records pertaining to the suspicious mammogram report and a medical history questionnaire. The participants will be followed after one year to capture progression or resolution of their suspicious mammogram report. After a biopsy confirms the diagnosis of cancer or benign lesion, a recut sample of the tissue may be requested for research.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Biomarkers

Detailed Description

Breast cancer is a leading cause of cancer mortality in women worldwide. According to estimates, approximately 46,000 women in the United States, and 130,000 women in the European Union, die due to breast cancer yearly. Early detection is of paramount importance in reducing mortality from this major public health burden. Screening mammography has been shown to reduce breast cancer mortality by 20% to 35% in women aged 40 to 69 years. Detection of small volume breast cancer at early stages is associated with a 10-year disease-free survival rate as high as 98% in patients with pT1a,bN0M0 tumors (measuring 1 cm or less, with disease-free axillary lymph nodes and no distant metastasis). The assumption that early diagnosis will lead to improved treatment outcomes has driven the search for diagnostic biomarkers.

Despite this enthusiasm, a biomarker for stage I breast cancer has been elusive. The predictive value of mammography declines in cohorts of patients with denser breast tissue and smaller lesions, and recent studies have indicated that the small amount of biomarker molecules emanating from a breast tumor of less than 1 cm is well below the sensitivity of detection for current analytical methods. In addition, biomarkers in body fluids are highly perishable. Biomarkers break down during collection, transport and storage due to endogenous degradative enzymes yielding false negatives. Thus there is a significant need for new technologies that will a) identify and measure low abundance biomarkers (less than 1 nanogram/mL), and b) is low cost and can be seamlessly integrated into the clinical workflow.

Primary Objective:

The primary goal of this study is to a) experimentally discover putative plasma markers for detecting early, stage I breast cancer in the setting of a suspicious mammogram and distinguish those cancers from benign lesions b) verify the putative markers through molecular profiling; and c) validate the markers by mass spectrometry.

Secondary Objectives:

1. Determine percent accuracy of breast cancer diagnosis in the context of 3D mammographically (screen detected) tumors.
2. Determine percent precision of cancer diagnosis in the context of 3D mammographically (screen detected) tumors.
3. Discover additional protein markers of early stage breast cancer that distinguish these tumors from benign lesions identified by mammography by comparing protein markers between patients with invasive cancer vs. benign tumors as determined by biopsy.
4. Additionally compare protein markers between patients with invasive cancer and pre-invasive neoplasms as determined by biopsy.
5. Bank samples for future research and sequencing.

• Study Type: Observational
• Enrollment (Anticipated): 270

Contacts and Locations

• Study Contact: Name: Mary Jo Bradley; Phone Number: 757-388-5629; Email: mxbradl1@sentara.com
• Study Contact Backup: Name: Kayla Kenke; Phone Number: 757-388-2406; Email: fkkenke@sentara.com

Study Locations

• United States
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Recruiting
      • Dorothy G Hoefer Comprehensive Breast Center
      • Principal Investigator: Richard Hoefer, DO
      • Contact: Kayla Kenke; Phone Number: 757-388-2406; Email: fkkenke@sentara.com
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Sentara Norfolk General Breast Center
      • Contact: Mary Jo Bradley; Phone Number: 757-388-5629; Email: mjbradl1@sentara.com
      • Contact: Kayla Kenke; Phone Number: 757-388-2406; Email: fkkenke@sentara.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All participants will be enrolled through direct contact with collaborating clinical sites. In the first phase this study will strive to enroll 150 participants who are identified as having a suspicious mammogram. Review of the data for the first set of 150 patients revealed a set of biomarkers discovered and evaluated blindly that showed a strong statistical correlation with cancer versus non cancer in the final pathologic diagnosis. Based on this success, a decision is made by the PI to extend the study to enroll an additional 120 patients.

Description

Inclusion Criteria:

• Women who receive a suspicious mammogram report or are scheduled to receive testing for suspect breast area, with a subsequent biopsy to confirm diagnosis
• Willingness and ability to donate biospecimens for the purpose of propelling research.
• Participants aged ≥ 18.

Exclusion Criteria:

• Individuals under 18 years of age or over 89 years of age.
• A known history of breast cancer.
• A diagnosis or history of any other type of cancer.
• Participants who are male.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Invasive Cancer; Invasive cancer confirmed by biopsy	Other: Biomarkers; Experimentally discover putative plasma markers for detecting early, stage I breast cancer in the setting of a suspicious mammogram and distinguish those cancers from benign lesions b) verify the putative markers through molecular profiling; and c) validate the markers by mass spectrometry.
Benign or pre-invasive lesion; Benign or pre-invasive lesion confirmed by biopsy	Other: Biomarkers; Experimentally discover putative plasma markers for detecting early, stage I breast cancer in the setting of a suspicious mammogram and distinguish those cancers from benign lesions b) verify the putative markers through molecular profiling; and c) validate the markers by mass spectrometry.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify markers to differentiate cancers from benign lesions	Experimentally discover putative plasma markers for detecting early, stage I breast cancer in the setting of a suspicious mammogram and distinguish those cancers from benign lesions, verify the putative markers through molecular profiling; and validate the markers by mass spectrometry.	Duration of Study, estimated 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Accuracy	1. Determine percent accuracy of breast cancer diagnosis in the context of 3D mammographically (screen detected) tumors.	1 week (from mammogram to biospy)
Determine Precision	2. Determine percent precision of cancer diagnosis in the context of 3D mammographically (screen detected) tumors.	1 week (from mammogram to biospy)
Discover additional protein markers	3. Discover additional protein markers of early stage breast cancer that distinguish these tumors from benign lesions identified by mammography by comparing protein markers between patients with invasive cancer vs. benign tumors as determined by biopsy.	Duration of Study, estimated 2 years
Compare protein markers	4. Additionally compare protein markers between patients with invasive cancer and pre-invasive neoplasms as determined by biopsy.	Duration of Study, estimated 2 years

Collaborators and Investigators

• Sponsor: Sentara Norfolk General Hospital
• Collaborators: George Mason University; Dorothy G. Hoefer Foundation
• Investigators: Principal Investigator: Richard Hoefer, DO, Sentara Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2017
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: May 1, 2017
• First Submitted That Met QC Criteria: May 8, 2017
• First Posted (Actual): May 10, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 16-09-EX-0146

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: No