Neoadjuvant Combined Endocrine and HER2 Target Therapy in Postmenopausal Women With ER and Her2 Positive Breast Cancer

• To evaluate the efficacy of the neoadjuvant combination therapy with letrozole and lapatinib in postmenopausal patients with ER-positive and HER2-positive breast cancer.
• 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)