Neoadjuvant Letrozole in Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative, Node Positive, Early-Stage Breast Cancer. (NELOPHER)

Neo-Adjuvant Endocrine Therapy in Post-Menopausal Hormone Receptor Positive HER 2 Neu Negative Node Positive Early-Stage Breast Cancer Patients With One Year of Letrozole.

The goal of this clinical trial is to learn whether letrozole, a hormone therapy drug, is effective in treating early-stage, hormone receptor-positive, HER2-negative breast cancer that has spread to nearby lymph nodes in postmenopausal women. The study will also evaluate the safety of taking letrozole for one year before surgery.

The main questions this study aims to answer are:

Can one year of letrozole eliminate cancer from the underarm (axillary) lymph nodes?

Can treatment with letrozole reduce the need for extensive lymph node surgery?

How safe and tolerable is long-term letrozole treatment?

This is a single-arm study, meaning all participants will receive letrozole. There is no placebo or comparison group.

Participants will:

Take letrozole 2.5 mg by mouth once daily for one year

Attend regular clinic visits for physical exams, blood tests, and imaging studies

Undergo surgery after completing treatment

Be followed for up to two years to monitor cancer recurrence and survival

Study Overview

• Status: Not yet recruiting
• Conditions: Hormone Receptor-Positive, HER2-Negative, Node Positive Breast Cancer
• Intervention / Treatment: Drug: Letrozole

Detailed Description

What is this study about?

This clinical trial is studying the use of letrozole, a hormone therapy medicine, in postmenopausal women with early-stage breast cancer that:

• Has spread to nearby lymph nodes,
• Is hormone receptor-positive (ER and/or PR positive), and
• Is HER2-negative. Letrozole is already widely used to treat hormone-positive breast cancer. In this study, it is given before surgery for a longer period than usual (one year) to see how well it works in shrinking cancer in the underarm (axillary) lymph nodes.

Why is this study being done? Many women with breast cancer that has spread to lymph nodes need axillary lymph node dissection (ALND), a surgery that removes many lymph nodes and can cause long-term side effects such as arm swelling (lymphedema), pain, and reduced arm movement.

This study aims to find out whether one year of letrozole treatment before surgery can:

• Eliminate cancer from the lymph nodes in some patients, and
• Reduce or avoid the need for extensive lymph node surgery.

Who can take part in this study?

Participants must:

• Be postmenopausal women aged 18-69 years,
• Have early-stage breast cancer (tumor size T1-T2),
• Have cancer in nearby lymph nodes (N1),
• Have hormone receptor-positive, HER2-negative breast cancer,
• Not have received prior chemotherapy or hormone therapy for this cancer. What treatment will participants receive?

All participants will receive:

• Letrozole 2.5 mg, taken once daily by mouth,
• For a total duration of one year before surgery. There is no placebo and no comparison group in this study.

What will happen during the study?

1. Screening and Baseline

   • Medical history, physical examination
   • Blood tests and breast/axillary imaging (ultrasound, mammography)
   • Confirmation of eligibility

2. Treatment Phase (1 year)

   • Daily oral letrozole
   • Regular follow-up visits for:

   Clinical assessments Imaging of lymph nodes Monitoring side effects

3. Surgery and Follow-up

   • Surgical evaluation of lymph nodes
   • Pathology testing to see if cancer remains
   • Follow-up for up to two years to monitor recurrence and survival

What are the main goals of the study? Primary goal

• To determine how many patients have no remaining cancer in the axillary lymph nodes (pathological complete response) after one year of letrozole treatment.
• To assess whether lymph node shrinkage may allow patients to avoid axillary lymph node dissection.

Secondary goals

• To measure:

  • Local or regional cancer recurrence,
  • Spread of cancer to distant organs,
  • Overall survival and disease-free survival,
  • Safety and side effects of long-term letrozole use.
• To evaluate how well ultrasound imaging predicts lymph node response to treatment.

How many participants will be included? A total of 126 patients will take part in this study.

Why is this study important?

If successful, this study may:

• Reduce the need for extensive lymph node surgery,
• Lower the risk of long-term surgical complications,
• Support a less invasive treatment approach for selected patients with hormone-positive breast cancer.

The results could help improve future treatment strategies for postmenopausal women with early-stage, node-positive breast cancer.

• Study Type: Interventional
• Enrollment (Estimated): 126
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr. Eram Akram; Phone Number: +923365163135; Email: umemustafa@hotmail.com

Study Locations

• Pakistan
  • Punjab Province
    • Lahore, Punjab Province, Pakistan, 54000
      • Cancer Care Hospital and Research Centre Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: Patients aged 18 to 69 years.
2. Menopausal Status: All patients must be postmenopausal, confirmed by serum estradiol levels or other clinical criteria.
3. Diagnosis: Histologically confirmed infiltrating ductal carcinoma of any grade.
4. Tumor Size: Primary tumor (T) category of T1 or T2 according to AJCC 8th edition, as measured by ultrasonography (USG) and mammography.
5. Node Involvement: N1 disease documented by clinical examination and USG, with histopathology confirmed by fine-needle aspiration cytology (FNAC) or core needle biopsy.
6. Hormone Receptor Status: Patients must be estrogen receptor (ER) positive and progesterone receptor (PR) positive/negative, with HER2 status negative.

Exclusion Criteria:

1. Age: Patients aged under 18 or over 69 years.
2. Tumor Size: Patients with a primary tumor larger than T2 >5cm or with N2 disease.
3. Histological Type: Infiltrating lobular carcinoma or other non-invasive breast cancer types.
4. Prior Treatments: Previous treatment with neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NACT).
5. Comorbidities: Significant comorbidities that preclude administration of anesthesia or compromise patient safety.
6. Disease Characteristics: Patients with multicentric or multifocal disease, as defined by imaging or histopathological findings.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Letrozole; Letrozole, Oral, 2.5mg daily, for 1 year	Drug: Letrozole; Letrozole is an oral aromatase inhibitor administered at a dose of 2.5 mg once daily for one year. It is used as neoadjuvant therapy in postmenopausal women with early-stage, hormone receptor-positive (ER+/PR+), HER2-negative, node-positive breast cancer to reduce tumor size and axillary lymph node involvement before surgery.; Other Names: Letrozole, Oral, 2.5mg daily, for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extent of Axillary Nodal Pathologic Complete Response (pCR)	Proportion of postmenopausal, hormone receptor-positive (ER+/PR+), HER2-negative, node-positive breast cancer patients achieving pathological complete response (pCR) in axillary lymph nodes after one year of neoadjuvant letrozole therapy, assessed by sentinel lymph node biopsy (SLNBx).	From baseline (pre-treatment) to the end of one-year letrozole treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loco-Regional Relapse Rate	Proportion of patients experiencing loco-regional recurrence (breast, chest wall, or axillary nodes) following one year of neoadjuvant letrozole therapy.	Assessed at 6, 12, and 24 months post-treatment initiation
Distant Relapse Rate	Proportion of patients developing distant metastases (e.g., bone, liver, lungs) after one year of neoadjuvant letrozole therapy.	Assessed at 6, 12, and 24 months post-treatment initiation
Safety and Tolerability	Frequency and severity of adverse events reported by participants or observed by investigators during letrozole therapy, categorized according to CTCAE v5.0.	Monitored continuously during the 1-year treatment period, reported at 3-month intervals.

Collaborators and Investigators

• Sponsor: Cancer Care Hospital & Research Centre Foundation, Lahore

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: January 31, 2026
• First Submitted That Met QC Criteria: January 31, 2026
• First Posted (Actual): February 6, 2026

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: HER2-Negative Breast Cancer; Node-Positive Breast Cancer; Early-Stage Breast Cancer; Hormone Receptor-Positive Breast Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Enzymes; Enzymes and Coenzymes; Nitriles; Triazoles; Oxidoreductases; Tumor Suppressor Proteins; Neoplasm Proteins; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Letrozole; WW Domain-Containing Oxidoreductase
• Other Study ID Numbers: CCH-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD will not be shared due to patient privacy and institutional data protection policies. Aggregate study results will be made publicly available through ClinicalTrials.gov and peer-reviewed publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No