Phase II Trial of Anti-HER2 Treatment in HER2-enriched Early Breast Cancer Identified by PAM50 (HER2E-PAM, PAMILIA Study)
In this study, we prospectively analyzed molecular subtyping through the PAM 50 test in HER2-negative (IHC1+ or 2+ (FISH/SISH-)) breast cancer patients. A phase 2 single arm study was designed to determine whether the addition of HER2-targeted treatment with treatment increases the pathologic remission rate.
• Pathologically and cytologically documented unsectable/metastatic breast cancer that :
• A. has confirmed HER2 negative expression regardless hormone receptor status
⁃ definition of HER2 negative breast cancer i) HER2 IHC 1+ without ISH or ii) HER2 IHC 2+ and ISH negative (average HER2 gene copy number \<4 signals/cell in single probe ISH or HER2/CEP17 ratio \<2.0 \& average HER2 gene copy number \<4 signals cell in dual-probe ISH)
• No prior treatment of stage II-III breast cancer
‣ HR+ \& HER2- breast cancer : cT1-4N1-3
⁃ HR- \& HER2- breast cancer : cT1N1-3 or cT2-4N0-3
• No systemic metastasis confirmed by pathological or radiological evaluation
• Patients over 19 years
• Confirmed to HER2-enriched subtype by PAM50 study
• Available FFPE 15-20 slides for evaluating PAM50 study
• ECOG 0-1
• Adequate bone marrow functions i) Hemoglobin≥ 9g/dL ii) ANC ≥1,500/mm3 iii) Platelet ≥100,000/mm3
• Adequate renal functions i) creatinine : ≤ 1.5 x UNL or ii) creatinine clearance (Ccr) ≥ 50 ml/min by Cockroft formula
⁃ Adequate liver functions i) Bilirubine : ≤ 1.5 x UNL ii) AST/ALT : ≤ 2.5 x UNL
⁃ Adequate cardiac functions
∙ LVEF ≥50% (with MUGA scan or TTE)
⁃ Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to first dose of study treatment.