Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether trastuzumab and letrozole are effective and safe in the preoperative treatment for postmenopausal patients with hormone receptor-positive and HER2-positive breast cancer.

Detailed Description
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Eligibility criteria Ages Eligible for Study: ≥ 20 years Invasive cancer (clinical stage IB-IIIB) Measurable tumor larger than 1cm ECOG status 0 or 1 Postmenopausal women Age ≥55 years and amenorrhea Age <55 years and amenorrhea for ≥12 months with FSH >30 mIU/ml HER2 positive tumor 3 positive on IHC 2 positive on IHC with HER2 gene amplification on FISH or SISH using a single-probe or dual-probe Estrogen receptor positive tumor Positive ER expression with Allred score more than PS3/TS8 or modified Allred score more than PS4/TS7 Eligible cardiac function Normal heard evaluated by ECG Consider clinically non-significant arrythmia and ischemic change as normal LVEF ≥ 55% measured by ECHO or MUGA scan Outcome measures Primary End-point The rate of pathologic complete response (pCR) No residual invasive cancer in breast Secondary End-point Clinical Response Rate Safety profiles for the preoperative use of concurrent trastuzumab and letrozole The rate of breast conservative surgery Total pathologic complete response (tpCR) No residual invasive cancer in breast and ipsilateral axilla Analysis of biomarkers based on baseline specimen and residual tumor Ki67 expression cDNA microarray: gene expression profiling Association between clinical response rate and circulating tumor cells (CTCs) CTCs are measured by CytoGen (SEOUL, KOREA)

Official Title
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A Phase II Trial of Preoperative HER2 Targeting and Endocrine Therapy in Postmenopausal Women With HER2 and HR Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Invasive cancer (clinical stage IB-IIIC) Measurable tumor larger than 1cm ECOG status 0 or 1 Postmenopausal women Age ≥55 years and amenorrhea Age <55 years and amenorrhea for ≥12 months with FSH >30 mIU/ml HER2 positive tumor 3 positive on IHC 2 positive on IHC with HER2 gene amplification on FISH or SISH using a single-probe or dual-probe Estrogen receptor positive tumor Positive ER expression with Allred score more than PS3/TS8 or modified Allred score more than PS4/TS7 Eligible cardiac function Normal heard evaluated by ECG Consider clinically non-significant arrythmia and ischemic change as normal LVEF ≥ 55% measured by ECHO or MUGA scan Exclusion Criteria: Inflammatory breast cancer Bilateral breast cancer Patients with previous breast cancer history Patients with previous breast cancer treatment: Generally include hormone therapy, chemotherapy, and radiotherapy) Patients having uncontrolled heart problems Ischemic heart disease within 6 months Congestive heart failure more than NYHA class II Unstable angina Clinically significant pericarditis Amyloid heart disease

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab and Letrozole<br>- Concurrently initiate two drugs on Day 1 of Cycle 1 | Drug: Trastuzumab<br>* - Eight times IV administration of trastuzumab per 3 weeks Trastuzumab 8mg/kg on Day 1 of Cycle 1 Trastuzumab 6mg/kg from Day 1 of Cycle 2 to Day 1 of Cycle 8<br>* Other names: Herceptin;Drug: Letrozole<br>* - Daily letrozole 2.5 mg/day for 24 weeks<br>* Other names: Femara;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of pathologic complete response | No residual invasive cancer in breast regardless of axilla | At time of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response Rate | Clinical response includes complete response, partial response and stable disease. | At time of surgery | 
| Safety profiles for the preoperative use of concurrent trastuzumab and letrozole | Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery | Up to 3 months after surgery | 
| The rate of breast conservative surgery | The rate of breast conservative surgery among the patients receiving surgery | Up to 3 weeks after surgery | 
| Total pathologic complete response (tpCR) | No residual invasive cancer in breast and ipsilateral axilla | At time of surgery | 
| Analysis of biomarkers based on baseline specimen and residual tumor | Ki67 expression cDNA microarray: gene expression profiling | Baseline and at time of surgery | 
| Association between clinical response rate and circulating tumor cells (CTCs) | Association between clinical response rate and circulating tumor cells (CTCs) : CTCs are measured by CytoGen (SEOUL, KOREA) | Baseline and at time of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ER, Breast cancer, HER2, Postmenopausal, Trastuzumab, Letrozole, Neoadjuvant endocrine treatment