Circulating Tumor DNA Based Minimal Residual Disease Detection for Patients With Early-Stage Breast Cancer

City of Hope

Status: Suspended

Conditions: HER2-Negative Breast Carcinoma; HER2-Positive Breast Carcinoma; Estrogen Receptor-Positive Breast Carcinoma; Triple-Negative Breast Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage I Breast Cancer AJCC v8

Treatments: Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Other: Survey Administration

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07136493

NCI-2025-05431 (Registry Identifier)

P30CA033572 (U.S. NIH Grant/Contract)

24463 (Other Identifier)

Details and patient eligibility

About

This clinical trial studies how well circulating tumor deoxyribonucleic acid (ctDNA) based minimal residual disease (MRD) detection works for patients with early-stage breast cancer. MRD refers to a very small number of tumor cells that remain in the body during or after treatment. ctDNA refers to small pieces of DNA that are released into a person's blood by tumor cells as they die. Management of patients after cancer surgery remains a clinical dilemma, particularly for cancer detected at earlier stages as many patients are cured by surgery alone. This results in very large clinical trials required to demonstrate a modest benefit from treatment. Using ctDNA MRD testing in early-stage breast cancer patients receiving standard treatment may help researchers identify groups that would benefit from additional therapy, leading to better outcomes.

Full description

PRIMARY OBJECTIVES:

I. To determine the pathologic response rate and presence of ctDNA post-neoadjuvant therapy in stage I-III breast cancer patients receiving neoadjuvant systemic therapy followed by curative-intent surgical resection, separately for Subgroup 1A: human epidermal growth factor receptor 2 positive (HER2+) (any estrogen receptor [ER]/progesterone receptor [PR] status) and Subgroup 1B: triple negative breast cancer (TNBC). (Cohort 1) II. To determine ctDNA detectability before and after curative-intent surgical resection in Cohort 2 ER+/any progesterone receptor (PR)/HER2- stage I-III breast cancer patients. (Cohort 2)

SECONDARY OBJECTIVES:

I. To determine ctDNA detectability before and after adjuvant chemotherapy and/or radiation therapy, by cohort and subgroup.

II. To determine ctDNA detectability during the follow-up period of up to 3 years after definitive treatment, by cohort and subgroup.

III. To describe, by cohort and subgroup, the association between detectable ctDNA measured post-neoadjuvant treatment and post-surgery with recurrence free survival (RFS).

IV. To describe, by cohort and subgroup, ctDNA levels at baseline and during neoadjuvant treatment and their association with clinical and pathologic response.

V. To describe, by cohort and subgroup, changes in ctDNA levels during systemic treatment (neoadjuvant and adjuvant) and association with clinical response determined radiographically.

VI. To describe, by cohort and subgroup, the difference in time between ctDNA detection (molecular recurrence) and radiographic evidence of disease recurrence following definitive treatment among patients who achieved undetectable ctDNA levels after surgery.

EXPLORATORY OBJECTIVE:

I. To explore the performance of up to two cancer detection assays - BestSEEK and enACT - in development by Dr. Tomasetti at TGen and City of Hope.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT 1: Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of standard of care (SOC) neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

COHORT 2: Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

Enrollment: 350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented written informed consent of the participant

• Age ≥ 18 years

• Diagnosis of stage I-III breast cancer (any gender)

• Malignancy must be epithelial. Non-epithelial breast malignancies such as lymphoma or sarcoma are not allowed

• Willingness to:

  • Provide blood samples
  • Provide archival tumor tissue sample (only necessary for Cohort 2 if analysis of surgical tissue was not successful)
  • Provide tumor tissue sample from resection/surgery (only necessary for Cohort 1 if analysis of surgical tissue was not successful)
  • Permit medical record review

• Fall into one of the following categories defined below: Cohort 1, Subgroup A or B OR Cohort 2

• COHORT 1: Must have archival diagnostic tissue available

• COHORT 1: Scheduled to undergo, but has not yet begun, neoadjuvant systemic therapy followed by curative resection

• COHORT 1 (Subgroup A): HER2+ by current American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guidelines (any ER/PR status)

• COHORT 1 (Subgroup B): Triple negative (ER, PR and HER2 negative). Defined as ER and PR ≤ 10% by immunohistochemistry (IHC) and HER2 negative, by current ASCO/CAP guidelines

• COHORT 2: Scheduled to undergo upfront curative surgical resection with or without adjuvant chemotherapy followed by adjuvant endocrine therapy

• COHORT 2: ER+/any PR/HER2- (ER positive defined as ER > 10% by IHC)

Exclusion criteria

• Ductal carcinoma in situ
• Inability to safely provide sequential blood samples
• Prior or concurrent invasive malignancy (unless disease free > 5 years)
• An employee who is under the direct/ indirect supervision of the principal investigator (PI)/ a co-investigator/ the study manager
• A direct study team member
• Inability to give informed consent

Trial design

Primary purpose: Screening

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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350 participants in 2 patient groups

Cohort 1 (blood collection for ctDNA testing - 1)

Experimental group

Description:

Patients undergo collection of blood samples for ctDNA testing at 14-21 days post cycle 1, day 1 of SOC neoadjuvant chemotherapy, on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

Treatment:

Procedure: Biospecimen Collection

Other: Survey Administration

Other: Electronic Health Record Review

Procedure: Biospecimen Collection

Cohort 2 (blood collection for ctDNA testing -2)

Experimental group

Description:

Patients undergo collection of blood samples for ctDNA testing on the day of SOC surgery, at 3-6 weeks after SOC surgery, at 1-2 weeks after SOC adjuvant radiation therapy (if receiving), at 2-4 weeks after SOC adjuvant systemic therapy (if receiving), every 3 months for 1 year after surgery, and then every 6 months up to year 3 after surgery. Patients may also undergo collection of tumor tissue during SOC surgery on study.

Treatment:

Procedure: Biospecimen Collection

Other: Survey Administration

Other: Electronic Health Record Review

Procedure: Biospecimen Collection