The Prospective Validation of Soluble Isoforms of ErbB2 (p105-sErB2) and EGFR (110kD-sEGFR) as Serum Markers of Efficacy in Hormone Sensitive Postmenopausal Women with Metastatic Breast Cancer Treated with Either Anastrozole Alone or in Combination with ZD1839 (IRESSA)
Co-Investigators
Elsa Cora, Ph.D., Associate Professor, Department of Biochemistry, University of Puerto Rico Medical Sciences Campus, Rio Piedras, Puerto Rico
Vicente Valero, M.D., Professor, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Massimo Cristofanilli, M.D., Associate Professor, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Our hypothesis is that soluble isoforms ErbB2 (p105-sErB2) and EGFR (110kD-sEGFR) are elevated in patients with advanced breast cancer. Particularly, the level of p105-sErB2 has been found to be elevated in patients with HER-2-overexpressing metastatic breast cancer and treatment with trastuzumab (Herceptin)-based regimens and has been associated with a reduction in measured levels. Furthermore, the reduction in the serum levels is predicted for response. The tissue level of expression of HER-2/neu and EGFR has been suggested to correlate with the development of endocrine-resistance. The use of selective inhibitors of the EGFR tyrosine kinase (e.g., ZD1839) can reverse the resistance to hormonal treatments (e.g., aromatase inhibitors and selective estrogen-receptor modulators). Hence, the clinical response to the hormonal agents can be improved upon combination with ZD1839 in postmenopausal women with hormone-sensitive metastatic disease. This randomized prospective trial will test this hypothesis and the measurement of the soluble forms of ErbB2 (p105-sErB2) and EGFR (110kD-sEGFR) can provide a useful surrogate marker of efficacy in those group of patients with possible predictive and progostic implications.
Specific Aims
- To evaluate the serum levels of soluble isoforms of ErbB2 (p105-sErB2) and EGFR (110kD-sEGFR) in patients newly diagnosed hormone-sensitive MBC
Hypothesis: p105-sErB2 110kD-sEGFR are elevated in patients hormone-receptor positive with recurrent, metastatic breast cancer.- Confirm the detection of p105-sErB2 and 110kD-sEGFR in circulating tumor cells at time of diagnosis of PBC
- Correlate with tissue expression of ErB-2 and EGFR
- To determine the modifications in serum levels of p105-sErB2 and 110kD-sEGFR during treatment with either anastrozole alone or the combination with ZD1839
Hypothesis: Response to treatment with either anastrozole alone (standard arm) or the combination with ZD1839 (investigational arm) is associated with reduced levels of p105-sErB2 and/or 110kD-sEGFR.- p105-sErB2 and/or 110kD-sEGFR can represent markers of efficacy in patients receiving these treatments
- Differential modifications in the levels of p105-sErB2 and 110kD-sEGFR can select patients that benefit from a target treatment (investigational arm)
- To determine correlations between variations in the serum levels of p105-sErB2 and/or 110kD-sEGFR and long-term outcome
Hypothesis: The persistence of elevated levels of p105-sErB2 and 110kD-sEGFR in either treatment arms indicate resistant disease. - Failure to reduce levels of p105-sErB2 and/or 110kD-sEGFR is associated with predictive and prognostic implications