Circulating Tumor DNA Dynamics to Optimize Neoadjuvant Therapy in HER2-Positive and Triple-Negative Breast Cancer (NEOSHED)

June 16, 2026 updated by: Grazia Arpino, Federico II University

Evaluation of Circulating Tumor DNA Dynamics for Treatment Optimization in Stage II-III HER2-Positive and Triple-Negative Breast Cancer Candidate to NAT

The purpose of this non-interventional, observational study is to evaluate the clinical utility of circulating tumor DNA (ctDNA) utility-specifically how quickly tumor DNA disappears from the bloodstream (ctDNA clearance)-to help monitor and predict treatment responses in patients with breast cancer.

The study focuses on patients diagnosed with Stage II to III HER2-positive or Triple-Negative Breast Cancer (TNBC) who are scheduled to receive standard neoadjuvant therapy (systemic treatment administered before surgery). Because these breast cancer subtypes involve different standard treatment regimens, the study prospectively stratifies patients into three distinct treatment cohorts (Cohorts A, B, and C) to match routine clinical practice and align blood sampling with meaningful clinical milestones.

Study Overview

Status

Not yet recruiting

Conditions

Study Type

Observational

Enrollment (Estimated)

186

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

The study population consists of female adult patients with newly diagnosed, histologically confirmed stage II-III HER2-positive or triple-negative breast cancer who are candidates for standard neoadjuvant therapy. Participants are selected and recruited from patients consecutively presenting to the outpatient oncology clinics and multidisciplinary breast cancer units at the University Hospital Federico II (Naples, Italy) and participating clinical centers. The cohort represents a real-world sample of patients undergoing routine clinical workup and standard-of-care neoadjuvant treatment regimens before scheduled surgical intervention.

Description

Inclusion Criteria:

  • Patients with documented stage II-III HER2+ or TNBC and fit candidates for NAT. 2. In TNBC group, confirmed negative ER, PR and HER2 disease by local testing on primary disease specimen: tumor must be negative ER, PR, and HER2 defined by immunohistochemistry (IHC) according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing (Allison et al., 2020; Wolff et al., 2023). 3. In HER2+ group, Confirmed HER2+ disease by local testing on primary disease specimen: tumour must be HER2+ according to ASCO/CAP 2023 guidelines for HER2 testing (Wolff et al., 2023). 4. Patients with measurable disease; Patients with multifocal or multicentric breast cancer with at least one tumor lesion ≥1.0 cm in the longest diameter by ultrasound (reference lesion) are also eligible if the two largest tumor lesions have been histologically confirmed in the clinical evaluation and meet pathological criteria for TNBC and HER2+. 5. No previous treatment of the disease by chemotherapy, hormone therapy, surgery or radiotherapy. 6. Patients with breast cancer are eligible for surgery. 7. Eastern Cooperative Oncology Group (ECOG) performance status≤2.

Exclusion Criteria:

  • 1. Patients with bilateral invasive BC. 2. Patients with metastatic BC (local spread to axillary lymph nodes is permitted (cN1_cN2a).

    3. Patients with inflammatory BC. 4. Patients with a known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including hepatitis. 5. Patients with a history of invasive BC, ductal carcinoma in situ or lobular carcinoma in situ, and other malignancy within 5 years prior to screening. 6. Patients with a documented history of haemorrhagic diathesis, coagulopathy, or thromboembolism. 7. Patients with known allergy or hypersensitivity to any of the study drugs or any of their excipients. 8. Patients with history of non-compliance to medical regimens. 9. Patients refusing to perform liquid and tissue biopsy. 10. Patients unwilling to or unable to comply with the protocol. 11. Patients having had major surgery within 14 days prior to screening. 12. Pregnant or lactating females prior to treatment. 13. Patients should be excluded if they have a known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cohort A
Patients with stage II-III HER2-positive or Triple-Negative Breast Cancer (TNBC) treated with standard sequential anthracycline-containing regimens
Cohort B
Patients with stage II-III HER2-positive breast cancer receiving a non-anthracycline neoadjuvant regimen based on the TRAIN-2 strategy
Cohort C
Patients with stage II-III HER2-positive breast cancer treated according to a TRYPHAENA-like regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Longitudinal assessment of ctDNA clearance (yes/no) across the three study cohorts following the completion of the first neoadjuvant treatment block. Clearance milestones are tailored to specific regimens: pre-anthracycline exposure for Cohort A, after 6
Time Frame: At the completion of neoadjuvant therapy Block 1 for each cohort (approximately 6 to 12 weeks from baseline, depending on the specific regimen schedule).
At the completion of neoadjuvant therapy Block 1 for each cohort (approximately 6 to 12 weeks from baseline, depending on the specific regimen schedule).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federico II University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

June 1, 2029

Study Registration Dates

First Submitted

June 16, 2026

First Submitted That Met QC Criteria

June 16, 2026

First Posted (Actual)

June 23, 2026

Study Record Updates

Last Update Posted (Actual)

June 23, 2026

Last Update Submitted That Met QC Criteria

June 16, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4870

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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