HER-2 gene amplification, HER-2 and epidermal growth factor receptor mRNA and protein expression, and lapatinib efficacy in women with metastatic breast cancer
Press MF et al. - Women with HER-2-positive metastatic breast cancer (BCa) benefit from lapatinib, whereas women with HER-2-negative metastatic BCa derive no incremental benefit from this treatment. Methods- Aim was to analyze the biomarkers from two randomized phase III trials to optimize selection of pts for lapatinib therapy
- Breast cancer tissue from EGF30001 and EGF100151 trials analyzed for:
- HER-2 gene amplification by FISH
- HER-2 mRNA by RT-PCR
- HER-2 protein expression by HercepTest IHC
- EGFR mRNA level by RT-PCR, and EGFR protein by IHC
- All compared with clinical outcomes
Results- HER-2 gene amplified in 47% and IHC was 3+ in 35%
- Positive EGFR immunostaining in 28% correlated with EGFR mRNA levels by RT-PCR
- HER-2 gene amplification/overexpression associated with improved clinical outcomes in both trials
- An improvement in outcome was seen in FISH-positive and IHC 0, 1+, or 2+ pts
- HER-2 mRNA expression correlated with HER-2 FISH and IHC status
- No correlation between EGFR expression and responsiveness to lapatinib regardless of HER-2 status
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