Neoadjuvant Trastuzumab and Letrozole for Postmenopausal Women (HERAKLES)

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

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.

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)"

- 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

Association between clinical response rate and circulating tumor cells (CTCs) : CTCs are measured by CytoGen (SEOUL, KOREA)"

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