Immune Response to Anti-HER2 Therapies in Patients With HER2-Positive Stage I-IV Breast Cancer
Study Details
Study Description
Brief Summary
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
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.
- 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:
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To estimate the proportion of patients who develop HER2-specific T cell and endogenous antibody responses.
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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.
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To determine if combination therapy induces immunity to common breast cancer associated antigens (i.e. CEA, IGFBP2, and P53).
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To determine if induction of HER2-specific T cell or antibody immunity is associated with improved progression-free and overall survival in patients.
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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.
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To determine whether anti-HER2 therapy induces HER2 loss and modulation of HER2-specific adaptive immune responses.
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To determine if loss-of-function mutations in antigen presenting genes are associated with recurrence in patients with HER2+ breast cancer.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Basic Science (biospecimen collection) 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
Undergo collection of blood and tumor tissue samples
Other Names:
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Outcome Measures
Primary Outcome Measures
- Correlation between HER2 specific T-cell response and clinical response [Up to 16 weeks]
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.
- Correlation between antibody response and clinical response [Up to 16 weeks]
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.
Other Outcome Measures
- Proportion of patients who develop HER2-specific T cell and endogenous antibody responses [Up to 16 weeks]
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.
- Levels of HER2 CD4 T-cells, HER2 CD8 T-cells, and HER2-specific antibodies [Up to 16 weeks]
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).
- Association between combination therapy and immunity to common breast cancer associated antigens [Up to 16 weeks]
Descriptive statistics will be used.
- Association between HER2-specific T cell or antibody immunity and improved progression-free survival [Up to 16 weeks]
Descriptive statistics will be used.
- Association between HER2-specific T cell or antibody immunity and improved overall survival in patients [Up to 16 weeks]
Descriptive statistics will be used.
- Association between anti-HER2 therapy and HER2 loss and modulation of HER2-specific adaptive immune responses [Up to 16 weeks]
Descriptive statistics will be used.
- Association between loss-of-function mutations and recurrence [Up to 16 weeks or recurrence]
Descriptive statistics will be used.
- Association between gene expression levels and recurrence [Up to 16 weeks or recurrence]
Descriptive statistics will be used.
- Association between Fc gamma receptor (R) or human leukocyte antigen (HLA) genotypes and ability to generate immunity [Up to 16 weeks]
Descriptive statistics will be used.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histological confirmed adenocarcinoma of the breast stage I-IV from the American Joint Committee on Cancer staging 8th edition
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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
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Scheduled to start new anti-HER2 therapy/therapies
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Provide written informed consent
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Willingness to provide blood samples for correlative research purposes
Exclusion Criteria:
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Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224-9980 |
Sponsors and Collaborators
- Mayo Clinic
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Saranya Chumsri, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MC1937
- NCI-2020-05781
- MC1937
- P30CA015083