Analysis of Letrozole in Patients With Operable Hormone Receptor Positive, HER2 Negative Breast Cancer

Study Overview
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Brief Summary
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This phase II trial examines letrozole in patients with newly diagnosed hormone receptor-positive HER2-negative invasive breast cancer that can be removed by surgery (operable). Letrozole is in a class of medications called nonsteroidal aromatase inhibitors. It works by decreasing the amount of estrogen produced by the body. This can slow or stop the growth of some types of breast cancer cells that need estrogen to grow.

Detailed Description
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PRIMARY OBJECTIVE: I. To comprehensively evaluate differences in tumor microenvironment subpopulations in aromatase inhibitor (AI)-sensitive versus (vs.) AI-resistant hormone receptor (HR)+ breast cancer. SECONDARY OBJECTIVES: I. To assess the effects of estrogen deprivation on the systemic immune response. II. To assess the effects of estrogen deprivation on tumor immune microenvironment. OUTLINE: Patients receive letrozole orally (PO) once daily (QD) for 2-8 weeks prior to surgery in the absence of disease progression or unacceptable toxicity. Patients then undergo collection of blood and tissue samples.

Official Title
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Comprehensive Single-Cell Transcriptional Analysis of Aromatase Inhibitor-Resistant Breast Cancer

Conditions
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Breast Adenocarcinoma, Invasive Breast Carcinoma, Resectable Breast Carcinoma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: SCREENING: Female >= 18 years Postmenopausal and suitable to receive aromatase inhibitor as per physician's discretion Histologically confirmed un-resected operable invasive adenocarcinoma of the breast ≥ 0.5 cm with estrogen receptor (ER) and/or progesterone receptor (PR) positive ≥ 10%, and no human epidermal growth factor receptor 2 (HER2) amplification or overexpression Patients must not have received any prior chemotherapy, radiation therapy, or endocrine therapy for their current breast cancer. Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included Willing and able to provide research tissue samples Willing and able to provide research blood samples Exclusion Criteria: Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive or those on chronic steroids NOTE: Must be off systemic steroids at least 14 days prior to pre-registration. However, topical steroids, inhalants or steroid eye drops are permitted Known history of active autoimmune disease that has required systemic treatment within =< 30 days (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) prior to pre-registration NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. Patients with vitiligo, Graves disease, or psoriasis not requiring systemic treatment within the past 30 days are not excluded. Patients with Celiac disease controlled with diet modification are not excluded

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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Design Details

Primary Purpose: Health Services Research
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (letrozole)<br>Patients receive letrozole PO QD for 2-8 weeks prior to surgery in the absence of disease progression or unacceptable toxicity. Patients then undergo collection of blood and tissue samples. | Procedure: Biospecimen Collection<br>* Undergo collection of blood and tissue samples<br>* Other names: Specimen Collection;Drug: Letrozole<br>* Given PO<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in tumor microenvironment subpopulations in aromatase inhibitor (AI)-sensitive version (vs.) AI-resistant hormone receptor (HR)+ breast cancer | Tissue samples from patients with early-stage hormone receptor-positive HER2-negative breast cancer will be collected to compare differences. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of estrogen deprivation on the immune microenvironment | Estrogen receptor will be evaluated by both biopsy and surgical specimens. | Up to 8 weeks | 
| Effects of estrogen deprivation on tumor immune microenvironment | Estrogen receptor will be evaluated by both biopsy and surgical specimens. | Up to 8 weeks |