Immune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer

Immune Response to Anti-HER2 Therapies

This study gathers information from the blood cells and tumor tissue during treatment with anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib, in patients with HER2 positive stage I-IV breast cancer who are scheduled to start anti-HER2 therapy. The information gained from this study may help researchers better understand the relation between cell response and anti-HER2 therapies.

Study Overview

• Status: Recruiting
• Conditions: Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Breast Adenocarcinoma; HER2-Positive Breast Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection

Detailed Description

PRIMARY OBJECTIVES I. To determine the correlation between HER2 specific T-cell response in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.

II. To determine the correlation between antibody response in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.

III. To determine the correlation between host immune response in tumor tissue in HER2-positive breast cancer patients with stage I-IV who receive anti-HER2 therapies, such as trastuzumab, pertuzumab, lapatinib, or neratinib and clinical responses.

EXPLORATORY OBJECTIVES:

I. To estimate the proportion of patients who develop HER2-specific T cell and endogenous antibody responses.

II. To examine within individual patients trends in levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies over the course of treatment.

III. To determine if combination therapy induces immunity to common breast cancer associated antigens (i.e. CEA, IGFBP2, and P53).

IV. To determine if induction of HER2-specific T cell or antibody immunity is associated with improved progression-free and overall survival in patients.

V. To determine if there are Fc gamma receptor (R) or HLA genotypes associated with the ability to generate immunity in response to anti-HER2 therapy.

VI. To determine whether anti-HER2 therapy induces HER2 loss and modulation of HER2-specific adaptive immune responses.

VII. To determine if loss-of-function mutations in antigen presenting genes are associated with recurrence in patients with HER2+ breast cancer.

VIII. To determine gene expression levels in tumors from patients who did not achieve pathologic complete response (pCR) that are associated with recurrence.

OUTLINE: This is an observational study. Patients are assigned to 1 of 2 cohorts.

BLOOD & TISSUE COHORT: Patients with stage I-III disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. Patients with stage IV disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of progressive disease. Patients with stage IV disease with no disease progression ≥ 2 years on the same line of therapy undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. For all patients, tissue samples from previous biopsy and/or surgical resection are also collected on study.

TISSUE-ONLY COHORT: For patients with stage I-IV disease who received or previously completed anti-HER2 therapy, tissue samples from previous biopsy and/or surgical resection are collected on study.

• Study Type: Observational
• Enrollment (Estimated): 230

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Recruiting
      • Mayo Clinic in Florida
      • Principal Investigator: Saranya Chumsri, MD
      • Contact: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Stage I-IV HER2 positive breast cancer patients

Description

Inclusion Criteria:

• Age >= 18 years
• Histological confirmed adenocarcinoma of the breast stage I-IV from the American Joint Committee on Cancer staging 8th edition
• Any estrogen receptor (ER) or progesterone receptor (PR) but HER2 positive defined as per the most current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline
• Provide written informed consent
• Willingness to provide blood samples for correlative research purposes
• BLOOD AND TISSUE COHORT: Scheduled to start new anti-HER2 therapy/therapies
• TISSUE-ONLY COHORT: Received or previously completed anti-HER2 therapy/therapies

Exclusion Criteria:

• Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive
• Receiving systemic steroid therapy or any other immunosuppressive therapy =< 30 days prior to registration. NOTE: Inhaled steroids, low-dose corticosteroids (e.g. equivalent to or less than oral prednisone 10 mg daily), and steroid use for primary prevention of nausea per institutional guidelines are allowed.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Observational Blood & Tissue Cohort; Patients with stage I-III disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. Patients with stage IV disease undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of progressive disease. Patients with stage IV disease with no disease progression ≥ 2 years on the same line of therapy undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence. For all patients, tissue samples from previous biopsy and/or surgical resection are also collected on study.	Procedure: Biospecimen Collection; Undergo collection of blood and tumor tissue samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection
Observational Tissue-Only Cohort; For patients with stage I-IV disease who received or previously completed anti-HER2 therapy, tissue samples from previous biopsy and/or surgical resection are collected on study.	Procedure: Biospecimen Collection; Undergo collection of blood and tumor tissue samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HER2 specific T-cell response and clinical response	Defined as (1) a 2-fold or greater increase in HER2-specific T cells or HER2-specific antibodies at any point during treatment if pre-treatment levels of HER2-specific T cells or antibodies are detectable, or (2) HER2-specific T cells or HER2-specific antibodies at any point during treatment if pretreatment levels of HER-2 binding activity are non-detectable.	Up to 16 weeks
Antibody response and clinical response	Defined as (1) a 2-fold or greater increase in HER2-specific T cells or HER2-specific antibodies at any point during treatment if pre-treatment levels of HER2-specific T cells or antibodies are detectable, or (2) HER2-specific T cells or HER2-specific antibodies at any point during treatment if pretreatment levels of HER-2 binding activity are non-detectable.	Up to 16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who develop HER2-specific T cell and endogenous antibody responses	A two sided alpha=0.10 test of proportions will be used to assess whether the proportion of women who develop a HER2-specific immune response differs between the women who develop a tumor response and those who do not.	Up to 16 weeks
Levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies	Descriptive statistics will be used to quantify T cell or antibody response within each cohort of patients, namely (neo)adjuvant vs. metastatic setting and within each anti-HER2 treatments (i.e. trastuzumab, pertuzumab, lapatinib, or neratinib).	Up to 16 weeks
Association between combination therapy and immunity to common breast cancer associated antigens	Descriptive statistics will be used.	Up to 16 weeks
Association between HER2-specific T cell or antibody immunity and improved progression-free survival	Descriptive statistics will be used.	Up to 16 weeks
Association between HER2-specific T cell or antibody immunity and improved overall survival in patients	Descriptive statistics will be used.	Up to 16 weeks
Association between anti-HER2 therapy and HER2 loss and modulation of HER2-specific adaptive immune responses	Descriptive statistics will be used.	Up to 16 weeks
Association between loss-of-function mutations and recurrence	Descriptive statistics will be used.	Up to 16 weeks or recurrence
Association between gene expression levels and recurrence	Descriptive statistics will be used.	Up to 16 weeks or recurrence
Association between Fc gamma receptor (R) or human leukocyte antigen (HLA) genotypes and ability to generate immunity	Descriptive statistics will be used.	Up to 16 weeks

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Saranya Chumsri, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2020
• Primary Completion (Estimated): July 27, 2028
• Study Completion (Estimated): July 27, 2028

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Estimated): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling
• Other Study ID Numbers: MC1937 (Mayo Clinic in Florida); NCI-2020-05781 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-011040 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No