Breast Cancer
Conditions
Keywords
Breast cancer, HER2, ER, Postmenopausal, Trastuzumab, Letrozole, Neoadjuvant endocrine treatment
Brief summary
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
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)
Interventions
DRUGTrastuzumab
\- 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
DRUGLetrozole
\- Daily letrozole 2.5 mg/day for 24 weeks
Sponsors
Seoul National University Hospital
Severance Hospital
Samsung Medical Center
Asan Medical Center
Gangnam Severance Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The rate of pathologic complete response | At time of surgery | No residual invasive cancer in breast regardless of axilla |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety profiles for the preoperative use of concurrent trastuzumab and letrozole | Up to 3 months after surgery | Toxicity according to CTCAE protocol from the initiated day to 3 months after surgery |
| The rate of breast conservative surgery | Up to 3 weeks after surgery | The rate of breast conservative surgery among the patients receiving surgery |
| Clinical Response Rate | At time of surgery | Clinical response includes complete response, partial response and stable disease. |
| Analysis of biomarkers based on baseline specimen and residual tumor | Baseline and at time of surgery | * Ki67 expression * cDNA microarray: gene expression profiling |
| Association between clinical response rate and circulating tumor cells (CTCs) | Baseline and at time of surgery | Association between clinical response rate and circulating tumor cells (CTCs) : CTCs are measured by CytoGen (SEOUL, KOREA) |
| Total pathologic complete response (tpCR) | At time of surgery | No residual invasive cancer in breast and ipsilateral axilla |
Countries
South Korea
Contacts
Primary ContactJoon Jeong, M.D.,Ph.D.
Backup ContactSung Gwe Ahn, M.D.
Outcome results
None listed