Development of a Horizontal Data Integration Classifier for Noninvasive Early Diagnosis of Breast Cancer

NCT04781062 | Unknown DMC

• 1 other identifier: 4452
• Study Type: interventional
• Target: 367
• Locations: 1 country
• Sites: 1

Brief Summary

This is a translational no-profit study. Our proposal aims at creating a noninvasive Horizontal Data Integration (HDI) classifier for early diagnosis of breast cancer, with the final goal of avoiding in most cases useless biopsies of suspect cases encountered during radiological screening. Women with radiologically identified lesions, BIRADS-3/4/5, smaller than 2 cm by radiological assessment (i.e., radiological T1), will be enrolled and invited to donate peripheral blood samples (35 ml) and urine samples (50 ml). Radiological images as well as demographic and anatomopathological data will be collected. Objective of this project is to develop a HDI classifier enabling early noninvasive diagnosis of breast cancer with similar accuracy compared to breast biopsies. Such classifier will be developed based on the correlation between the molecular profile of peripheral blood (ctDNA, proteins, exosomes) and urine (ctDNA) collected at T0 (baseline, before diagnostic biopsy) and bioptic diagnosis. The assessment of the profile of peripheral blood (ctDNA, proteins, exosomes) and urine (ctDNA) at two time points for diagnosed pT1 breast cancers (T0: baseline, before biopsy; T1: after diagnosis of pT1 breast cancer) will allow us to distinguish between tumor- and host-specific molecular alterations in connection with the presence/absence of breast cancer.

Conditions

Breast Cancer

Keywords

Translational Study; Horizontal Data Integration Classifier

Outcome Measures

Primary Outcomes (1)

• Development of a HDI classifier enabling early noninvasive diagnosis of breast cancer with similar accuracy compared to breast biopsies

  Accuracy of a horizontal data integration (HDI) classifier in correctly classifying pT1 breast cancers from benign lesions (i.e., non-invasive breast adenocarcinoma) presenting with similar radiological features (i.e., maximum lesion diameter smaller or equal to 2 cm). The HDI classifier is defined as a variable mixture of features from different radiomics analyses on baseline mammograms and molecular analyses on peripheral blood (ctDNA methylation by cfMeDIPSeq, proteins using the SomaScan® Somalogic platform, miRNA sequencing from exosomes) and urine (ctDNA methylation by cfMeDIPSeq) collected at T0 (baseline, before diagnostic biopsy). This outcome will be compared with the accuracy of diagnostic biopsy on the same patients' cohort.

  5 years

Secondary Outcomes (2)

• Accuracy of the HDI classifier

  5 years

• Analytical and clinical validity of the HDI classifier

  5 years

Study Arms (2)

Breast Cancer Stage T1 Group

EXPERIMENTAL

Women with radiologically identified lesions, BIRADS-3/4/5, smaller than 2 cm by radiological assessment (i.e., radiological T1), will be enrolled and invited to donate peripheral blood samples and urine samples at baseline. Radiological images as well as demographic and anatomopathological data will be collected. If bioptically confirmed T1 breast cancer, patients will undergo a second peripheral blood and urine collection after primary breast cancer surgery.

Diagnostic Test: Blood and urine molecular analysis (Timing 0); Diagnostic Test: Blood and urine molecular analysis (Timing 1)

Benign Breast Lesion Group

ACTIVE COMPARATOR

Women with radiologically identified lesions, BIRADS-3/4/5, smaller than 2 cm by radiological assessment (i.e., radiological T1), will be enrolled and invited to donate peripheral blood samples and urine samples at baseline. Radiological images as well as demographic and anatomopathological data will be collected. If bioptically confirmed benign lesion, no other samples will be collected.

Diagnostic Test: Blood and urine molecular analysis (Timing 0)

Interventions

Blood and urine molecular analysis (Timing 0) DIAGNOSTIC_TEST

peripheral blood and urine sample collection

Benign Breast Lesion Group; Breast Cancer Stage T1 Group

Blood and urine molecular analysis (Timing 1) DIAGNOSTIC_TEST

peripheral blood and urine sample collection

Breast Cancer Stage T1 Group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Breast lesions detected by digital bilateral mammography
• Eligible for diagnostic biopsy (tru-cut or VABB) as per normal clinical practice
• Ability and willfulness to comply with the protocol requirements

You may not qualify if:

• Previous history of cancer, any type
• Clinical or radiological suspicion of advanced or metastatic cancer at the time of screening
• Known history of active or treated autoimmune or manifest chronic or seasonal and active allergic disorders
• History of major trauma or surgery during the 24 weeks before screening
• History of active infectious disease, either chronic or acute but occurring during the 8 weeks before screening
• History of known acute or chronic cardiac, kidney, or liver disease disorders or acute cardiac events

Sponsors & Collaborators

• Ospedale Policlinico San Martino: lead
• Associazione Italiana per la Ricerca sul Cancro: collaborator
• Universita degli Studi di Genova: collaborator
• Sidra Medicine: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (1)

Ospedale Policlinico San Martino

Genova, 16132, Italy

Location

Related Publications (1)

• Ravera F, Cirmena G, Dameri M, Gallo M, Vellone VG, Fregatti P, Friedman D, Calabrese M, Ballestrero A, Tagliafico A, Ferrando L, Zoppoli G. Development of a hoRizontal data intEgration classifier for NOn-invasive early diAgnosis of breasT cancEr: the RENOVATE study protocol. BMJ Open. 2021 Dec 31;11(12):e054256. doi: 10.1136/bmjopen-2021-054256.

  PMID: 34972769 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gabriele Zoppoli, MD, PhD

  Ospedale Policlinico San Martino

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Based on the results of breast lesion biopsy, patients are assigned to two different groups: * Breast Cancer Stage T1 Group * Benign Breast Lesion Group

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: March 4, 2021
• Study Start: January 19, 2021
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2024
• Last Updated: November 1, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)