This is a prospective, multicenter, cohort study aiming to explore the cardiotoxicity of targeted therapy for HER-2 positive breast cancer patients who lives in high altitude area. One hundred and thirty two HER-2 positive breast cancer patients who will receive neoadjuvant, adjuvant, or palliative targeted therapy will be enrolled. The cardiotoxicity of targeted therapy will be observed and recorded during the treatment and one year after the end of treatment. The subjects will be stratified by age, baseline cardiac risk factors, and anthracyclines.

HER-2 positive breast cancer patients who live at high altitudes greater than 2000 meters for long periods of time and will receive trastuzumab-based targeted therapy will be enrolled. The subjects included early and advanced patients. Treatment regimens includes chemotherapy combined with trastuzumab, chemotherapy combined with trastuzumab and pertuzumab, trastuzumab alone, and trastuzumab plus pertuzumab. Electrocardiogram, cardiac ultrasound, NT-proBNP, and TNI will be tested every 3 months when the treatment begins. The primary endpoint is cardiotoxity. The second endpoints is pathologic complete response (pCR) rate in neoadjuvant therapy, objective remission rate (ORR) and disease control rate (DCR) in neoadjuvant and palliative therapy.

Inclusion Criteria:

1. Histologically confirmed invasive HER2-positive breast cancer.
2. The baseline left ventricular ejection fraction >55%.
3. Living at high altitude area （>2000 meters）for at least 10 years.
4. ECOG score 0-2.
5. Expected survival time ≥ 12 months.

Exclusion Criteria:

1. Patients with previous breast cancer or other malignant tumor within 5 years.
2. Patients who had accepted previous anti-HER2 or anthracyclines-based therapy.
3. Patients with severe heart disease or discomfort.
4. Patients who are pregnant.
5. Patients with other conditions considered not suitable to be enrolled by the investigator.

All enrolled patients are from four centers of Qinghai province.