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

Phase 2

Terminated

• Conditions: Breast Adenocarcinoma; Invasive Breast Carcinoma; Resectable Breast Carcinoma
• Interventions: Procedure: Biospecimen Collection; Drug: Letrozole

• Registration Number: NCT05447910
• Lead Sponsor: Mayo Clinic

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-06-28
• Study First Submitted QC: 2022-07-01
• Study First Posted: 2022-07-07
• Study Start: 2022-07-21
• Primary Completion: 2023-09-27
• Study Completion: 2023-09-27
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-21
• Last Update Posted: 2025-02-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 21

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (letrozole)	Biospecimen Collection	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.
Treatment (letrozole)	Letrozole	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Effects of estrogen deprivation on the immune microenvironment	Up to 8 weeks	Estrogen receptor will be evaluated by both biopsy and surgical specimens.
Effects of estrogen deprivation on tumor immune microenvironment	Up to 8 weeks	Estrogen receptor will be evaluated by both biopsy and surgical specimens.

Trial Locations

Locations (1)

Mayo Clinic in Florida; 🇺🇸 Jacksonville, Florida, United States