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)"

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