Biopsy of Calcifications Under Contrast Enhancement Guide (BoCCE)

NCT04862429 | Active Not Recruiting

• 1 other identifier: BoCCE
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Calcification clusters are 30-40% of recalls in mammographic screening, but have a low positive predictive value (\~15%) for ductal cancer in situ (DCIS) or invasive cancer. These calcifications often need histological assessment with stereotaxic guided biopsy (Mammotome). With extended calcifications, choosing the best area to biopsy may be challenging. The main objective of this 1:1 randomized controlled clinical trial is to compare the accuracy of the CESM guide (study arm with biopsy under CESM guidance) with the traditional Mammotome (control arm with biopsy under stereotactic guidance) in conducting the biopsy in the area of greatest malignancy/grade of the lesion, using as gold-standard the histological exam of the operating piece. Women recalled with indication to perform stereotactic biopsy for clusters of suspicious calcifications on mammography (BIRADS R3 or R4 or R5) not mass-associated will be included. Anticipated sample size is 100 women per arm.

Conditions

Breast Cancer; Calcification

Keywords

biopsy; contrast enhanced mammography; calcification

Outcome Measures

Primary Outcomes (1)

• Distance in mm between the biopsy site and the area of greatest malignancy/grade in the operating piece.

  In patients sent to surgery, the main outcome will be determined on the operating piece by a single pathologist operating in blind, which will assess the type of lesion (B1-B5), invasiveness, grade, the extent of the lesion in mm, the percentage of invasive component, the distance in mm between the location of the biopsy and the area of greatest malignancy (DCIS G3 or invasive component). In patients not sent to surgery, the outcome will be determined by following the patients for a follow-up of at least 24 months, verifying if they have undergone surgery on that specific lesion during the follow-up (in particular if they have developed B5 lesions in situ or invasive in that location).

  Cross-sectional: the reference standard will be collected during surgery, usually 3 to 6 weeks after biopsy. In any case, it cannot be collected more than 6 months after biopsy.

Secondary Outcomes (7)

• Proportion of patients needing contrast imaging

  Cross-sectional: the reference standard will be collected during surgery, usually 3 to 6 weeks after biopsy. In any case, it cannot be collected more than 6 months after biopsy.

• Diagnosis upgrading

  Cross-sectional: the reference standard will be collected during surgery, usually 3 to 6 weeks after biopsy. In any case, it cannot be collected more than 6 months after biopsy.

• Biopsy sensitivity

  The reference standard will be collected during surgery, usually 3 to 6 weeks after biopsy. Women not needing surgery (negative at biopsy) will be followed up for 24 months in orther to assess the presence of cancers.

• Waiting time between biopsy and surgery

  The outcome measure is the time from biopsy to first surgical intervention, usually this time is in the range of 3 to 6 weeks.

• Accuracy for lesion size

  Cross-sectional: the reference standard will be collected during surgery, usually 3 to 6 weeks after biopsy. In any case, it cannot be collected more than 6 months after biopsy.

Study Arms (2)

Contrast enhanced mammography guided biopsy

EXPERIMENTAL

Patients will be subjected to CESM; the two orthogonal mammographic projections, after intravenous administration of iodized contrast-enhancement (Omnipaque), will be performed. Surgical and medical treatments will be defined accordingly to the imaging and histological findings obtained with the experimental procedure.

Other: Contrast enhanced mammography guided biopsy (diagnostic procedure)

mammography guided biopsy

ACTIVE COMPARATOR

Patients will be subjected to stereotactic biopsy Mammotome as normal clinical practice. Surgical and medical treatments will be defined accordingly to the imaging and histological findings obtained with the standard procedure.

Other: Mammography guided biopsy (diagnostic procedure)

Interventions

Contrast enhanced mammography guided biopsy (diagnostic procedure) OTHER

With visible contrast-enhancement, stereotactic biopsy will be performed under CESM guidance. After administration of an additional dose of iodized contrast-enhancement (Omnipaque), the insertion of the biopsy needle and the biopsy sampling will be targeted on the area of greatest enhancement in the context of calcifications. In the absence of contrast-enhancement, stereotactic biopsy Mammotome will be performed, using X-ray guidance. The insertion of the biopsy needle and biopsy will be targeted on the most suspicious calcification cluster or area. At the end of the procedure, a metal clip marker will be placed in the biopsy site; the placement will be verified with dual orthogonal mammography projection (as regular clinical practice).

Also known as: Contrast enhanced spectral mammography guided biopsy

Contrast enhanced mammography guided biopsy

Mammography guided biopsy (diagnostic procedure) OTHER

For all lesions, stereotactic biopsy Mammotome will be performed, using X-ray guidance. The insertion of the biopsy needle and biopsy will be targeted on the most suspicious calcification cluster or area. At the end of the procedure, a metal clip marker will be placed in the biopsy site; the placement will be verified with dual orthogonal mammography projection (as regular clinical practice).

Also known as: stereotactic biopsy

mammography guided biopsy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women with positive mammography for calcifications without mass, requiring biopsy
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with clinical mammography and screening recalls with mammographic confirmation of clusters of suspicious calcifications (BIRADS R3 or R4 or R5) not mass-associated will be included, with indication to perform stereotactic biopsy, evaluated at the Breast Care Facility of AUSL-IRCCS in Reggio Emilia.

You may not qualify if:

• Women with contraindication to the administration of iodized contrast medium will be excluded.

Sponsors & Collaborators

• Azienda USL Reggio Emilia - IRCCS: lead
• General Electric: collaborator

Study Sites (1)

Azienda USL - IRCCS di Reggio Emilia

Reggio Emilia, RE, 42123, Italy

Location

Related Publications (6)

• Narayan AK, Keating DM, Morris EA, Mango VL. Calling all calcifications: a retrospective case control study. Clin Imaging. 2019 Jan-Feb;53:151-154. doi: 10.1016/j.clinimag.2018.09.016. Epub 2018 Oct 5.

  PMID: 30340079 BACKGROUND

• Si J, Guo R, Huang N, Xiu B, Zhang Q, Chi W, Wu J. Axillary evaluation is not warranted in patients preoperatively diagnosed with ductal carcinoma in situ by core needle biopsy. Cancer Med. 2019 Dec;8(18):7586-7593. doi: 10.1002/cam4.2623. Epub 2019 Oct 29.

  PMID: 31660702 BACKGROUND

• Jakub JW, Murphy BL, Gonzalez AB, Conners AL, Henrichsen TL, Maimone S 4th, Keeney MG, McLaughlin SA, Pockaj BA, Chen B, Musonza T, Harmsen WS, Boughey JC, Hieken TJ, Habermann EB, Shah HN, Degnim AC. A Validated Nomogram to Predict Upstaging of Ductal Carcinoma in Situ to Invasive Disease. Ann Surg Oncol. 2017 Oct;24(10):2915-2924. doi: 10.1245/s10434-017-5927-y. Epub 2017 Aug 1.

  PMID: 28766196 BACKGROUND

• Grimm LJ, Ryser MD, Partridge AH, Thompson AM, Thomas JS, Wesseling J, Hwang ES. Surgical Upstaging Rates for Vacuum Assisted Biopsy Proven DCIS: Implications for Active Surveillance Trials. Ann Surg Oncol. 2017 Nov;24(12):3534-3540. doi: 10.1245/s10434-017-6018-9. Epub 2017 Aug 9.

  PMID: 28795370 BACKGROUND

• Cheung YC, Tsai HP, Lo YF, Ueng SH, Huang PC, Chen SC. Clinical utility of dual-energy contrast-enhanced spectral mammography for breast microcalcifications without associated mass: a preliminary analysis. Eur Radiol. 2016 Apr;26(4):1082-9. doi: 10.1007/s00330-015-3904-z. Epub 2015 Jul 10.

  PMID: 26159872 BACKGROUND

• Iotti V, Ragazzi M, Besutti G, Marchesi V, Ravaioli S, Falco G, Coiro S, Bisagni A, Gasparini E, Giorgi Rossi P, Vacondio R, Pattacini P. Accuracy and Reproducibility of Contrast-Enhanced Mammography in the Assessment of Response to Neoadjuvant Chemotherapy in Breast Cancer Patients with Calcifications in the Tumor Bed. Diagnostics (Basel). 2021 Mar 4;11(3):435. doi: 10.3390/diagnostics11030435.

  PMID: 33806306 BACKGROUND

Related Links

• European guidelines on breast cancer screening and diagnosis

MeSH Terms

Conditions

Breast Neoplasms; Calcinosis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Pierpaolo Pattacini, MD

  AUSL-IRCCS Reggio Emilia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Pathology results will be blindly reviewed by external pathologists.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Test and treat randomized trial.

Study Record Dates

• First Submitted: April 21, 2021
• First Posted: April 28, 2021
• Study Start: July 24, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2025
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Seven years since publication of the result about main outcome.
• Access Criteria: A request to Area Vasta Emilia Nord Ethic Committee should be submitted.

Locations

IT (1)