Impact of Neoadjuvant Chemotherapy on the Peripheral Blood Immune Phenotype in Operable Breast Cancer, the ENHANCE Study

Study Overview
=================
Brief Summary
-----------------
This early phase I trial evaluates the impact of chemotherapy before surgery (neoadjuvant) on the peripheral blood immune phenotype in patients with operable breast cancer. Collecting blood and information from patients with breast cancer may help to understand how the immune system influences response to treatment, and how the immune system reacts to breast cancer treatment.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To evaluate whether pre-neoadjuvant chemotherapy (NAC) peripheral blood immune phenotypes (defined by mass cytometry) are associated with pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with operable breast cancer. II. To evaluate whether the baseline peripheral blood immune phenotype differs between patients with breast cancer and age-matched healthy controls. SECONDARY OBJECTIVES: I. To characterize changes in the baseline peripheral blood immune phenotype that arise as a consequence of neoadjuvant chemotherapy. II. To create a biorepository of peripheral blood samples for future research in breast cancer, including circulating tumor deoxyribonucleic acid (ctDNA), epigenetic and functional studies. EXPLORATORY OBJECTIVE: I. To evaluate differences in peripheral blood immune phenotype of patients with oligometastatic breast cancer compared to patients with stage I-III breast cancer. OUTLINE: Patients undergo blood sample collection at baseline (prior to first NAC treatment), after taxane and prior to first dose of anthracycline/cyclophosphamide (A/C) (for patients receiving a taxane), end of NAC, 1-4 weeks and 6 months post-surgery. Patients also undergo tissue collection at 1-4 weeks and 6 months post-surgery. After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Official Title
-----------------
Evaluating the Impact of Neoadjuvant Chemotherapy on the Peripheral Blood Immune Phenotype in Patients With Operable Breast Cancer (ENHANCE)

Conditions
-----------------
Invasive Breast Carcinoma

Intervention / Treatment
-----------------
* Procedure: Biospecimen Collection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >= 18 years Histologically confirmed, operable, invasive breast cancer. Note: Patients with oligometastatic breast cancer (up to 3 isolated distant metastases) will be eligible after review and approval by principal investigator (PI) Recommended to receive neoadjuvant systemic treatment by their primary medical oncologist and planning to receive one of the regimens Provide written informed consent Willing to return to Mayo Clinic for breast cancer surgery Willingness to provide mandatory blood specimens for future research on breast cancer at Mayo Clinic Exclusion Criteria: Patients who have already initiated neoadjuvant chemotherapy for the current malignancy Inability to provide blood samples based on the judgement of the treating physician Inability to comply with the protocol Patient is pregnant or plans to become pregnant

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Basic science (biospecimen collection)<br>Patients undergo blood sample collection at baseline (prior to first NAC treatment), after taxane and prior to first dose of A/C (for patients receiving a taxane), end of NAC, 1-4 weeks and 6 months post-surgery. Patients also undergo tissue collection at 1-4 weeks and 6 months post-surgery. | Procedure: Biospecimen Collection<br>* Undergo blood and tissue collection<br>* Other names: Specimen Collection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of peripheral blood immune phenotypes with pathological complete response | For each of the ten unique family subtypes, and individual cell population within a histological subtype, will utilize a logistic regression model to identify those markers measured at baseline that are predictive of achieving a pathological complete response. Will also perform classification and regression trees (CART) modeling to get at the interplay of the markers (i.e. cell subtypes), which are all uniformly expressed as percentages. | Up to 5 years | 
| Difference of peripheral blood immune phenotypes | Will be assessed between patients with breast cancer and age-matched healthy controls. Will compare the average difference in the baseline marker expression between the cases and age-matched healthy controls using a two-sample t-test. The two-sample t-test will be used to test the null hypothesis of no difference in means against the alternative hypothesis that there is a difference in means; the two-sided P-value will be reported. Will also perform CART modeling as in the first co-primary objective to get at the interplay of the markers. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in baseline peripheral blood immune phenotype as a consequence of neoadjuvant chemotherapy (NAC) | Will calculate the absolute change for each of the 30 markers, including grouped by the ten unique family subsets. In this largely descriptive analysis, within each histologic subtype, the expression levels will be graphically displayed over time (e.g. plotting the median at each of the three occasions, as well as plotting the mean change from baseline at post-NAC and post-surgery; the patient-level trajectories will be superimposed. Because this is a hypothesis generating objective, all data will be graphed and tabulated and any inferential statistics calculated will be limited and should be interpreted with caution. | Baseline up to 2-4 weeks post-surgery |