Lesion Composition and Quantitative Imaging Analysis on Breast Cancer Diagnosis

The objective is to better identify suspicious breast lesions that need to be biopsied for malignancy in women currently recommended for biopsy. The long-term goal is to reduce unnecessary biopsies and increase biopsy yield. To do this, the investigators have developed an innovative way to use FDA-approved breast imaging protocols to acquire multispectral images to measure the composition of suspicious breast lesions. The central hypothesis is that breast tissue composition in combination with analysis of morphological and textural tissue characteristics on digital breast tomosynthesis (DBT) imaging will yield significantly higher breast cancer specificity than conventional interpretation of DBT alone.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: q3CB

Detailed Description

Women with dense breast have not been shown to benefit by increased cancer detection of volumetric digital breast tomosynthesis (DBT) but may benefit by lower recall rates. DBT screening biopsy rates are similar to 2D digital mammography; higher for first screening exams, lower thereafter with adjustment for age and breast density. In the U.S., 71% of biopsies do not result in a breast cancer diagnosis among women ages 40-79 who undergo breast cancer screening. To address the high rate of unnecessary biopsies, an innovative way to use FDA-approved breast imaging protocols has been developed to acquire multispectral images to measure the lipid/water/protein (L/W/P) composition of suspicious breast lesions. Malignant breast tissue has unique L/W/P composition fractions when compared to normal or benign breast tissue. This proposal aims to increase biopsy yield (BI-RADS-PPV3) through combining L/W/P biological biomarkers with quantitative morphological and textural image analysis. This combination of composition and physical descriptions of suspicious breast lesions is called q3CB. The benefits of adding q3CB to the current DBT screening/diagnostic imaging paradigm, that may already include computer aided detection, is not known. This study is designed to compare the expected biopsy yield with and without q3CB in a clinical reader study and explore how q3CB may be combine with existing technologies. The central hypothesis is that biological L/W/P fractions in breast tissue in combination with analysis of morphological and textural tissue characteristics will yield significantly higher breast cancer specificity than conventional interpretation of DBT alone. The objective is to better identify suspicious breast lesions that need to be biopsied for malignancy in women currently recommended for biopsy. The long-term goal is to reduce unnecessary biopsies and increase biopsy yield. The investigators rationale for the proposed research is that biological L/W/P descriptions of breast lesions will lead to more specific biopsy decisions and a better understanding of cancer types. Specifically, the project aims are 1) develop q3CB lesion signatures for distinguishing breast cancer lesions from benign lesions, using 600 prospectively-acquired DBT exams of women recommended to undergo biopsy; 2) conduct a clinical reader study to compare radiologists' performance on standard-of-care FFDM or DBT without and with the inclusion of q3CB signatures; 3) Investigate the utility of q3CB lesion signatures in a screening paradigm to improve sensitivity and specificity on CADe-identified suspicious lesions in the tasks of assessing malignancy as well as in associating with their association with cancer subtypes; Exploratory) explore the added sensitivity and specificity of dual-energy DBT in phantom studies that explore lesion size, composition, and breast density. The innovation of this study is the full characterization of lipid/water/protein lesion composition with DBT and how it complements existing computer aided diagnostic programs paired with clinical radiologists providing evidence ready for clinical translation of this unique and emerging technology.

• Study Type: Observational
• Enrollment (Anticipated): 600

Contacts and Locations

• Study Contact: Name: John A Shepherd, PhD; Phone Number: 808-440-5234; Email: johnshep@hawaii.edu
• Study Contact Backup: Name: Leila Kazemi; Phone Number: 808-440-5231; Email: lkazemi@hawaii.edu

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center & Research Institute, Inc.
      • Contact: Emily Research Services Project Coordinator; Phone Number: 813-745-5501; Email: emily.amato@moffitt.org
      • Principal Investigator: Bethany L Niell, MD
      • Principal Investigator: Dana K Ataya, MD
  • Hawaii
    • Hilo, Hawaii, United States, 96720
      • Recruiting
      • Hawaii Radiology Associates, LTD (East Hawaii Women's Imaging Center)
      • Contact: Scott Grosskreutz, MD; Phone Number: 808-935-1825
      • Principal Investigator: Scott Grosskreutz, MD
    • Honolulu, Hawaii, United States, 96822
      • Recruiting
      • The Queen's Medical Center
      • Contact: Richmond Clinical Research Associate; Phone Number: 808-691-7609; Email: riwong@queens.org
      • Principal Investigator: Todd Seto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

All 600 women will be recruited and enrolled from one of three sites: Queen's Medical Center (Honolulu, HI), East Hawaii Women's Imaging Center (Hilo, HI), and H. Lee Moffitt Cancer Center & Research Institute (Tampa, FL).

Description

Inclusion Criteria:

• Had a recent diagnostic mammogram with a BI-RADS diagnostic score 4 or 5 assigned by a radiologist (BIRADS are standardized mammography assessment categories: 4 is for "Suspicious abnormality", 5 is for "Highly suggestive of malignancy".
• Have not had biopsy

Exclusion Criteria:

• Pregnant or breast feeding
• History of breast cancer or a mastectomy (removal of the breast) with Systemic Therapy (ex. Chemotherapy, hormones and hormone inhibitors, etc.).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify biological composition of lesions	Quantify the biological composition (lipid/water/protein) of suspicious lesions.	Baseline
Quantify morphology of lesions	Quantify morphology/texture (radiomics) of suspicious lesions.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of radiologists' image interpretations with and without q3CB signatures	Difference in AUC between the "1st read" and "2nd read" image interpretations. In the "1st read," they will be provided with the FFDM/DBT images and in the "2nd read," they will also be provided with the ncCEM q3CB composition and radiomics signature (likelihood of malignancy).	Baseline
Sensitivity and Specificity of readers' responses for the BI-RADs assessment categories	Sensitivity and specificity values will be calculated: a BI-RADS assessment of 4a or higher (i.e., 4a, 4b, 4c, and 5) defined a positive call for cancer diagnosis and, conversely, a BI-RADS assessment of 3 or lower (i.e., 3, 2, and 1) defined a negative call for cancer diagnosis.	Baseline

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: H. Lee Moffitt Cancer Center and Research Institute; Queen's Medical Center; Hawaii Radiologic Associates, Ltd.
• Investigators: Principal Investigator: John A Shepherd, PhD, University of Hawaii Cancer Research Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2022
• Primary Completion (ANTICIPATED): July 1, 2025
• Study Completion (ANTICIPATED): July 1, 2026

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (ACTUAL): May 11, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 2, 2023
• Last Update Submitted That Met QC Criteria: January 31, 2023
• Last Verified: January 1, 2023

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: SHEPHERD-2021-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No