Breast CancerNCT02743910
Monitoring Plasma Tumor DNA in Early-Stage Breast Cancer
An observational study of Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
This study is being done to see if it is possible to use blood samples to predict response to treatment in breast cancer patients receiving preoperative (or neoadjuvant) therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- ptDNA and Tissue sample
- How many people
- 228 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to 2 Mar 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Newly diagnosed invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT)
Who may be able to join
- Newly diagnosed, histologically confirmed invasive breast cancer that is triple negative (estrogen receptor [ER], progesterone receptor [PR], and HER2-neu negative) or HER2-positive (any ER/PR status)
- Unresected, untreated breast cancer that is T2, T3, or T4a-c; any N (nodal status); and M0 (not metastatic)
- ECOG Performance Status of 0 or 1
- Planning to receive a neoadjuvant chemotherapy regimen containing a taxane ± an anthracycline for at least 4 cycles. Patients with HER2-positive disease must also be planning to receive HER2-targeted therapy.
- Diagnostic tumor material must be available for correlative analyses
- Patients must have the ability to understand and the willingness to sign a written informed consent document
Who cannot join
- No prior treatment for the current breast cancer, though prior use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) for the prevention of breast cancer is acceptable.
- Women who are pregnant or nursing are excluded.
- No history of another primary malignancy in the last 5 years prior to registration. Patients with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287
About this study
Official title: Plasma Tumor DNA and Pathologic Complete Response in Early-Stage, High-Risk Breast Cancer
This study is being done to see if it is possible to use blood samples to predict response to treatment in breast cancer patients receiving preoperative (or neoadjuvant) therapy. Research has shown that most breast cancers release tumor-specific DNA into the blood (that is, DNA that is specific to the tumor cells or cancer). This DNA can be detected in blood testing known as plasma tumor-DNA or "ptDNA." This DNA is separate from that found in the blood and tissue samples which serve as the "instruction book" or "genetic code" for the cells that make-up the human body. The changes in ptDNA before and after treatment, as well as after surgery, may also help investigators to understand more about a patient's risk of cancer returning and long-term outcomes.
Read the detailed description
This is a prospectively designed study. Up to 229 newly diagnosed invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT) will be enrolled. Blood samples will be collected pre-operatively at the time of diagnosis/prior to NAT, post-cycle 1/pre-cycle 2 of NAT, after all NAT/immediately before surgery, and post-operatively at 6, 12, 24, and 36 months, and annually thereafter if funding allows. Researchers will also collect representative tissue samples from the diagnostic biopsy (in all participants) and definitive surgery (if available). Additionally, to look at feasibility of tumor DNA analyses in urine samples, urine samples will be collected along with blood samples (urine tumor DNA or utDNA).
Next generation sequencing will be performed on core biopsies of all enrolled patients for tumor-specific mutations (TSM) discovery. Based on those findings, droplet digital PCR (ddPCR) on plasma DNA samples will also be performed to confirm the presence of the TSM in the plasma on diagnosis, and one TSM will be chosen to track as the plasma tumor DNA (ptDNA) mutation of interest. Investigators will perform ddPCR on pre-operative plasma DNA samples and will assess for the presence of ptDNA. Pathologists will assess surgical specimens for pathologic response (such as complete response/pCR and residual cancer burden/RCB). As primary endpoint, investigators will assess the number of patients with and without preoperative ptDNA who have pCR versus residual disease. As exploratory endpoints, the following will also be performed: (a) quantitative multiplex methylation-specific PCR (QM-MSP) in diagnostic biopsy and definitive residual surgery specimen; and, (b) the circulating methylated tumor DNA (cMethDNA) assay in plasma specimens (baseline and after NAT), and evaluate associations with pathologic response.
Additional endpoints include the association between plasma and tissue markers at baseline, after NAT, and (if available) during surveillance with long-term prognosis (invasive disease-free survival/IDFS and distant disease-free survival/DDFS).
- Conditions
- Breast Cancer
- Being tested
- ptDNA, Tissue sample
- Keywords
- preoperative, neoadjuvant, plasma tumor DNA, ptDNA
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ptDNAOther
Also called Blood sample
Pre-operative blood samples for ptDNA will be collected at the time of diagnosis/prior to NAT, post-cycle 1/pre-cycle 2 of NAT, after all NAT/immediately before surgery, and post-operatively at 6, 12, 24, and 36 months, and annually thereafter if funding allows.
Tissue sampleOther
Representative tissue sample will be collected from the diagnostic biopsy (in all participants) and definitive surgery (if available)
| Study group | Role | What they receive |
|---|---|---|
| Stage II-III breast cancer | Up to 229 newly diagnosed stage II-III invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT) will be enrolled. ptDNA blood samples as well as a representative tumor tissue sample from both the diagnostic and surgical procedure (if available) will be collected. Receives: Other: ptDNA; Other: Tissue sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of absence of plasma tumor DNA (ptDNA) with pathologic complete response (pCR)
To estimate the negative predictive value (NPV) of the absence of plasma tumor DNA (ptDNA) Tumor Specific Mutations (TSMs) after neoadjuvant therapy (NAT) for the absence of residual disease as defined by pathologic complete response (pCR) in stage II-III HER2-positive or triple negative breast cancer (TNBC)
NPV = True Negative/True Negative + False Negative (probability that the disease is not present when the test is negative)
Measured: 6 months
Secondary outcomes (2)
Prognostic value of ptDNA for invasive disease-free survival and distant disease-free survival
To estimate the prognostic value of ptDNA for 5-year invasive disease-free survival (IDFS) and distant disease-free survival (DDFS) in TNBC patients following completion of loco-regional and systemic therapy
Measured: 5 years
Correlation of absence of ptDNA with residual cancer burden (RCB)
To estimate the NPV of the absence of ptDNA TSMs after NAT for the absence of residual disease as defined by residual cancer burden (RCB) 0 or 1
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2016 (estimated)
- Study startJul 2016
- Primary completionFeb 2019
- Study completion2 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 228 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium
- Responsible party
- Sponsor
- Investigators
- Antonio C Wolff, M.D., Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02743910
- Sponsor's protocol ID
- TBCRC040
- Other IDs
- TBCRC 040, IRB00093688
- Status last verified
- Jul 2026
- First submitted
- 15 Apr 2016
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hunter NB, Parsons HA, Cope L, Canzoniero JV, Navarro FCP, El-Refai S, Anampa JD, Sparano JA, Rimawi M, Storniolo AM, Mainor C, Nanda R, DeMichele A, Gupta GP, Stringer-Reasor EJ, Lynce F, Cobain EF, Puhalla S, Jankowitz R, Rexer B, Mayer I, Hwang ES, Blackwell K, El Ayass W, Lee Y, Tweed C, Wilkinson M, Pennisi A, Sun B, Wright P, Gralow JR, Chen R, Boyle SM, Stearns V, Wolff AC, Park BH. The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease. J Clin Oncol. 2026 May 10;44(14):1283-1295. doi: 10.1200/JCO-25-02934. Epub 2026 Mar 10.
PubMed 41805422
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Tumor DNA and Pathologic Complete Response in Early-Stage, High-Risk Breast Cancer
- ClinicalTrials.gov ID
- NCT02743910
- Acronym / sponsor ID
- TBCRC040
- Conditions
- Breast Cancer
- Keywords
- preoperative, neoadjuvant, plasma tumor DNA, ptDNA
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 228 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium
- Study start
- Jul 2016
- Primary completion
- Feb 2019 (actual)
- Study completion
- 2 Mar 2026 (actual)
- First posted
- 19 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done to see if it is possible to use blood samples to predict response to treatment in breast cancer patients receiving preoperative (or neoadjuvant) therapy. Research has shown that most breast cancers release tumor-specific DNA into the blood (that is, DNA that is specific to the tumor cells or cancer). This DNA can be detected in blood testing known as plasma tumor-DNA or "ptDNA." This DNA is separate from that found in the blood and tissue samples which serve as the "instruction book" or "genetic code" for the cells that make-up the human body. The changes in ptDNA before and after treatment, as well as after surgery, may also help investigators to understand more about a patient's risk of cancer returning and long-term outcomes.
Detailed description
This is a prospectively designed study. Up to 229 newly diagnosed invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT) will be enrolled. Blood samples will be collected pre-operatively at the time of diagnosis/prior to NAT, post-cycle 1/pre-cycle 2 of NAT, after all NAT/immediately before surgery, and post-operatively at 6, 12, 24, and 36 months, and annually thereafter if funding allows. Researchers will also collect representative tissue samples from the diagnostic biopsy (in all participants) and definitive surgery (if available). Additionally, to look at feasibility of tumor DNA analyses in urine samples, urine samples will be collected along with blood samples (urine tumor DNA or utDNA).
Next generation sequencing will be performed on core biopsies of all enrolled patients for tumor-specific mutations (TSM) discovery. Based on those findings, droplet digital PCR (ddPCR) on plasma DNA samples will also be performed to confirm the presence of the TSM in the plasma on diagnosis, and one TSM will be chosen to track as the plasma tumor DNA (ptDNA) mutation of interest. Investigators will perform ddPCR on pre-operative plasma DNA samples and will assess for the presence of ptDNA. Pathologists will assess surgical specimens for pathologic response (such as complete response/pCR and residual cancer burden/RCB). As primary endpoint, investigators will assess the number of patients with and without preoperative ptDNA who have pCR versus residual disease. As exploratory endpoints, the following will also be performed: (a) quantitative multiplex methylation-specific PCR (QM-MSP) in diagnostic biopsy and definitive residual surgery specimen; and, (b) the circulating methylated tumor DNA (cMethDNA) assay in plasma specimens (baseline and after NAT), and evaluate associations with pathologic response.
Additional endpoints include the association between plasma and tissue markers at baseline, after NAT, and (if available) during surveillance with long-term prognosis (invasive disease-free survival/IDFS and distant disease-free survival/DDFS).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stage II-III breast cancer | – | Other: ptDNA, Other: Tissue sampleUp to 229 newly diagnosed stage II-III invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT) will be enrolled. ptDNA blood samples as well as a representative tumor tissue sample from both the diagnostic and surgical procedure (if available) will be collected. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Newly diagnosed invasive HER2-positive or triple-negative breast cancer patients planning neoadjuvant therapy (NAT)
Key inclusion criteria (6 listed)
- Newly diagnosed, histologically confirmed invasive breast cancer that is triple negative (estrogen receptor [ER], progesterone receptor [PR], and HER2-neu negative) or HER2-positive (any ER/PR status)
- Unresected, untreated breast cancer that is T2, T3, or T4a-c; any N (nodal status); and M0 (not metastatic)
- ECOG Performance Status of 0 or 1
- Planning to receive a neoadjuvant chemotherapy regimen containing a taxane ± an anthracycline for at least 4 cycles. Patients with HER2-positive disease must also be planning to receive HER2-targeted therapy.
- Diagnostic tumor material must be available for correlative analyses
Key exclusion criteria (3 listed)
- No prior treatment for the current breast cancer, though prior use of selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) for the prevention of breast cancer is acceptable.
- Women who are pregnant or nursing are excluded.
- No history of another primary malignancy in the last 5 years prior to registration. Patients with prior history of in situ cancer or basal or localized squamous cell skin cancer are eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ptDNAAlso: Blood samplePre-operative blood samples for ptDNA will be collected at the time of diagnosis/prior to NAT, post-cycle 1/pre-cycle 2 of NAT, after all NAT/immediately before surgery, and post-operatively at 6, 12, 24, and 36 months, and annually thereafter if funding allows. | Other | Stage II-III breast cancer |
| Tissue sampleRepresentative tissue sample will be collected from the diagnostic biopsy (in all participants) and definitive surgery (if available) | Other | Stage II-III breast cancer |
Primary outcome
Correlation of absence of plasma tumor DNA (ptDNA) with pathologic complete response (pCR)
Time frame: 6 months
To estimate the negative predictive value (NPV) of the absence of plasma tumor DNA (ptDNA) Tumor Specific Mutations (TSMs) after neoadjuvant therapy (NAT) for the absence of residual disease as defined by pathologic complete response (pCR) in stage II-III HER2-positive or triple negative breast cancer (TNBC) NPV = True Negative/True Negative + False Negative (probability that the disease is not present when the test is negative)
2 secondary outcomes
Prognostic value of ptDNA for invasive disease-free survival and distant disease-free survival
Time frame: 5 years
Correlation of absence of ptDNA with residual cancer burden (RCB)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2026.
- Derived from this study: PubMed 41805422Hunter NB, Parsons HA, Cope L, Canzoniero JV, Navarro FCP, El-Refai S, Anampa JD, Sparano JA, Rimawi M, Storniolo AM, Mainor C, Nanda R, DeMichele A, Gupta GP, Stringer-Reasor EJ, Lynce F, Cobain EF, Puhalla S, Jankowitz R, Rexer B, Mayer I, Hwang ES, Blackwell K, El Ayass W, Lee Y, Tweed C, Wilkinson M, Pennisi A, Sun B, Wright P, Gralow JR, Chen R, Boyle SM, Stearns V, Wolff AC, Park BH. The Pathologic Response Evaluation and Detection in Circulating Tumor-DNA Study: Ultrasensitive Circulating Tumor-DNA Assessment of Breast Cancer Minimal Residual Disease. J Clin Oncol. 2026 May 10;44(14):1283-1295. doi: 10.1200/JCO-25-02934. Epub 2026 Mar 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio C Wolff, M.D. study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation of absence of plasma tumor DNA (ptDNA) with pathologic complete response (pCR) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02743910, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2026.