Cross-talk between epidermal growth factors and the ER occurs at multiple levels and seems to play a crucial role in breast cancer progression and endocrine resistance.Combined HER1/HER2-targeted therapy with aromatase inhibitors for ER-positive and HER-2 positive postmenopausal breast cancer might enhance response and block emergence of endocrine resistant tumor.

1. To evaluate the efficacy of the neoadjuvant combination therapy with letrozole and lapatinib in postmenopausal patients with ER-positive and HER2-positive breast cancer.
2. To assess markers predictive of treatment response and outcome in this setting.

Inclusion Criteria:

• Written informed consent
• Female patients
• Histologically confirmed invasive breast cancer
• Primary tumor greater than 2cm diameter, measured by sonography
• N0-3 (any N if resectable) and no evidence of distant metastasis (M) (isolated supraclavicular node involvement allowed)
• ER positive (intermediate and strong positive)
• HER2 positive (IHC3+ or FISH positive in case of IHC 2+)
• No evidence of metastasis (M0)
• No prior hormonal, chemotherapy or radiotherapy is allowed
• No breast operation other than biopsy to make diagnosis is allowed
• Postmenopausal women with ECOG Performance Status of 0 or 1
• Postmenopausal, as defined by any of the following:
• At least 55 years of age
• Under 55 years of age and amenorrheic for at least 12 months OR follicle-stimulating hormone (FSH) values ≥ 30 IU/L and estradiol levels ≤ 20 IU/L
• Prior bilateral oophorectomy or prior radiation castration with amenorrhea for at least 6 months
• Adequate hematopoietic, renal, hepatic function:

Exclusion Criteria:

• Patients who received hormonal, chemotherapy or radiotherapy for breast cancer
• Patients who underwent surgery for breast cancer
• Patients with bilateral invasive breast cancer
• Patients with inflammatory breast cancer (T4d)
• Patients without primary tumor (T0) Inability to perform [18F]FES PET imaging due to physical inability, claustrophobia, or other mental illness.
• ER poor disease as defined locally (e.g: Allred score 1-3, H-score<100)
• Patients who have history of cancer other than in situ uterine cervix cancer or non-melanotic skin cancer
• Chronic daily treatment with aspirin (>325mg/day) or clopidogrel (>75mg/day)
• Chronic daily treatment with corticosteroids (dose of >10mg /day ethylprednisolone equivalent)
• Clinically significant cardiovascular disease: CVA/stroke (<6month prior to enroll), MI (<6month prior to enroll), unstable angina, NYHA Grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication.
• Hormone replacement therapy within 4 weeks of starting treatment
• Known hypersensitivity to any of the study drugs including ditosylate monohydrate salt
• Pregnant or nursing mother (if applicable)