To assess the clinical efficacy, biologic effects and safety of the EGFR inhibitor erlotinib in the treatment of patients with 'triple receptor-negative' metastatic carcinoma of the breast.
Primary endpoints:
1). time to progression (TTP)
Secondary endpoints:
1). clinical benefit rate as defined by complete and partial response and stable disease
2). overall survival (OS)
3). safety profile and tolerability of erlotinib
4). biologic correlative studies
Correlative studies:
1). EGFR protein positivity
2). EGFR gene copy number and sequencing
3). Assessment of markers of epithelial-mesenchymal transition (e.g. vimentin, E cadherin)
4). Degree of phosphorylation of the EGFR
5.) Expression, degree of phosphorylation and activation of downstream mediators of the EGFR e.g. AKT, mTor, GSK3, p70S6kinase, 4E-BP1, ribosomal S6 protein, ERK2, p38, and JNK, as well as other downstream pathway proteins including inhibitory proteins such as PTEN and LKB1
6). Changes in the expression and phosphorylation of the markers listed in number 4 above during therapy.
7). transcriptional and protein array on frozen tissues which are available
8). comparative genomic hybribization (CGH) on frozen tissues which are available |