Adjuvant Dual Anti-HER2 Therapy in Patients With Small, Node-negative, HER2-positive Breast Cancer

Inclusion criteria

• Women aged 18-70 years old
• Have finished radical operation
• Histologically confirmed invasive ductal carcinoma (IDCA)
• According to AJCC ,pT<8mm, pN0, no evidence for metastasis
• Operation specimens are available for ER, progesterone receptor (PR) and HER2 detection, patients should be HER2 positive tumor (IHC staining of 3+ [uniform, intense membrane staining of >30% of invasive tumor cells], or a FISH result of .6 HER2 gene copies per nucleus or a FISH ratio [HER2 gene signals to chromosome 17 signals] of >2.2), nuclear grade 3.
• Should have tumor tissue available and sufficient for multi-spots sampling.
• It has been <84 days since the date of definitive surgery, and there is adequate wound healing as determined by the Treating Physician.
• Has Eastern Cooperative Oncology Group (ECOG) Performance Score 0-1, expected survival time > 12 months
• Cardiac function had to be within normal limits (left ventricular ejection fraction [LVEF] ≥50%), as established by multiple gated acquisition scan or echocardiography.
• Adequate bone marrow function, adequate liver and renal function, and adequate coagulation function.
• Women with potential child-bearing must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable and effective method of contraception to avoid pregnancy during the study.
• Written informed consent according to the local ethics committee requirements.

Exclusion criteria

• pT≥8mm or node positive
• Metastatic breast cancer
• Any prior systemic or loco-regional treatment of breast cancer, including chemotherapy in 28 days
• With a history of malignant tumor except uterine cervix cancer in situ or skin basal cell carcinoma
• Patients with medical conditions that indicate intolerant to adjuvant target therapy and related treatment, including severe infection, coagulation disorder, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease
• Has symptomatic peripheral neuropathy > grade 2 according to NCI
• Known severe allergy to any drugs in this study
• Has cardiac dysfunction or lung dysfunction defined as follows:

• grade ≥3 CHF according to NCI CTCAE v 5.0 or NYHA≥II
• angina which requires drug control, cardiac infraction, and any other vascular disease with apparent clinical symptoms
• uncontrolled high-risk arrhythmia
• uncontrolled hypertension
• Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive
• Patient is pregnant or breast feeding