Trial of Afatinib With Paclitaxel for Neoadjuvant Therapy of TNBC and Research of Biomarkers of Afatinib

Inclusion Criteria

• •1. Female patients, age ≥20 years
• •2. Histologically confirmed invasive ER-, PR-, and HER2-negative (triple-negative) adenocarcinoma of the breast
• •3. Triple-negative tumors are defined as:
• •i. For HER2-negative: Fluorescence in situ hybridization (FISH)-negative (defined by ratio \<2.0) or Immunohistochemical (IHC) 0, IHC 1+, or IHC 2+ or IHC 3+and FISH-negative (defined by ratio \<2.0) ii. For ER- and PR-negative: \< 5% tumor staining by immunohistochemistry (IHC)
• •4. The first TNBC 20 patients with or without EGFR expression or mutation are eligible. Interim analysis of response rate will be calculated to determine the criteria of 21 to 40 patients.
• •5. All of the newly diagnosed TNBC patients should be met the following criteria: clinical node-positive with any T stage patents or clinical node-negative patients with cT2-4. cT1N0M0 lesions are excluded. Patients with metastatic disease are excluded. The measurement method of tumor size can be by physical exam and/or image study.
• •6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1.
• •7. Within 2 weeks prior randomization:
• •i. Adequate bone marrow function, hepatic function, and renal function. ii. Controlled blood pressure with or without antihypertensive treatment iii. Normal prothrombin time (PT) and partial thromboplastin time (PTT) iv. Adequate cardiac function assessed by 12-lead ECG and if clinically indicated echocardiography to document LVEF
• •9. Adequate bone marrow function defined as WBC ≥3.5 x 109/L, ANC ≥1.5 x 109/L, platelets ≥LLN, and hemoglobin ≥10 g/dL.
• •10. Adequate liver function defined as total serum bilirubin ≤1.5X ULN and serum transaminases ≤2.5X ULN
• •11. Adequate renal function defined as creatinine ≤1.5X ULN
• •12. Able and willing to give informed consent and comply with the protocol
• •13. Written informed consent obtained prior to any Screening/baseline procedures
• •14. Knowledge of the investigational nature of the study and ability to provide consent for study participation; and ability and willingness to comply with study visits, treatment, testing, and other study procedures