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

Study Overview
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Brief Summary
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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.

Detailed Description
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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. 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: Patients undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence for patients with stage I-III, or progressive disease for patients with stage IV. Patients with stage IV HER2 positive breast cancer with no disease progression >= 2 years on the same line of therapy, undergo blood sample collection at baseline anytime during their treatment with anti-HER2 therapies, 8 and 16 weeks after the first blood draw, and at the time of invasive disease recurrence. Patients also undergo tumor tissue collection for the evaluation of gene expression and deoxyribonucleic acid (DNA) variants.

Official Title
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Immune Response to Anti-HER2 Therapies

Conditions
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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, Prognostic Stage I Breast Cancer AJCC v8, Prognostic Stage II Breast Cancer AJCC v8, Prognostic Stage III Breast Cancer AJCC v8, Prognostic Stage IV Breast Cancer AJCC v8

Intervention / Treatment
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* Procedure: Biospecimen Collection


Participation Criteria
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Eligibility Criteria
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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 3+ staining intensity (on a scale of 0 to 3) by means of immunohistochemistry (IHC) analysis OR gene amplification on fluorescence in situ hybridization (FISH) ratio >= 2.0 Scheduled to start new anti-HER2 therapy/therapies Provide written informed consent Willingness to provide blood samples for correlative research purposes 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Basic science (biospecimen collection)<br>Patients undergo collection of blood samples at baseline, 8 and 16 weeks after starting treatment, and at the time of invasive disease recurrence for patients with stage I-III, or progressive disease for patients with stage IV. Patients with stage IV HER2 positive breast cancer with no disease progression >= 2 years on the same line of therapy, undergo blood sample collection at baseline anytime during their treatment with anti-HER2 therapies, 8 and 16 weeks after the first blood draw, and at the time of invasive disease recurrence. Patients also undergo tumor tissue collection for the evaluation of gene expression and DNA variants. | Procedure: Biospecimen Collection<br>* Undergo collection of blood and tumor tissue samples<br>* Other names: Specimen Collection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between 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 | 
| Correlation between 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 |