HER2陽性ステージI～IV乳癌患者における抗HER2療法に対する免疫反応

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.