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

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

The purpose of this study is to study to collect tissue samples from patients with early stage hormone receptor-positive HER2-negative breast cancer.

Study Overview

• Status: Terminated
• Conditions: Invasive Breast Carcinoma; Breast Adenocarcinoma; Resectable Breast Carcinoma
• Intervention / Treatment: Procedure: Biospecimen Collection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 21
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with early-stage hormone receptor-positive HER2-negative breast cancer

Description

Inclusion Criteria:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with early-stage hormone receptor-positive HER2-negative breast cancer receiving letrozole; Patients undergo collection of blood and tissue samples prior to beginning treatment with letrozole and at least two weeks after the start of letrozole treatment, but prior to surgery.	Procedure: Biospecimen Collection; Undergo collection of blood and tissue samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Saranya Chumsri, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2022
• Primary Completion (Actual): September 27, 2023
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: June 28, 2022
• First Submitted That Met QC Criteria: July 1, 2022
• First Posted (Actual): July 7, 2022

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 11, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Skin Diseases; Breast Diseases; Carcinoma; Breast Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Aromatase Inhibitors; Letrozole
• Other Study ID Numbers: 21-003046; NCI-2022-04802 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No