[2034] Serum EGFR and HER-2 levels in metastatic breast cancer patients receiving gefitinib therapy.
Allen CL, Chapman CJ, Hitch A, Agrawal A, Cheung KL, Robertson JFR.. University of Nottingham, Nottingham, United Kingdom; City Hospital, Nottingham, United Kingdom
Introduction: Epidermal growth factor receptor (EGFR) and HER-2/neu are highly homologous members of the cerbB receptor family. Both are pivotal in cell signalling pathways and breast carcinogenesis. HER-2 gene amplification is seen in 20-30% of breast cancers and it is linked to a more aggressive disease state and a poorer prognosis. Serum HER-2/neu levels are routinely measured to monitor Herceptin therapy. EGFR is a target for Gefitinib, a current anti-EGFR therapy. However the value of serum EGFR in predicting therapeutic response and survival in breast cancer is unknown.
Aims: To investigate the independent and additive roles of serum EGFR and HER-2/neu levels in a panel of metastatic breast cancer patients, and their role in predicting therapeutic response and overall patient survival.
Patients and Methods: Serial serum samples were taken from 32 metastatic breast cancer patients receiving 250-500mg/day Gefitinib (Iressa
, Astra-Zeneca, UK), in a phase II trial. All patients were categorised according to UICC criteria and divided into 2 cohorts, clinical benefit (CB=9) (complete response + partial response + stable disease >6 months) or progressive disease (PD=23) (progression in <6 months). Serum EGFR levels were determined using a commercial immunoassay (Oncogene Science Bayer corporation) and HER-2/neu levels were determined using the ADVIA Centaur automated HER-2/neu immunoassay. Statistical analysis was carried out using a paired samples t-test.
Results:
| HER-2 | EGFR | ||||||
| Pre - 6wks | Pre - Pro | 6wks - Pro | Pre - 6wks | Pre - Pro | 6wks - Pro | ||
| CB ER+ (n=9) | 3 | 6 | 6 | 5 | 5 | 7 | |
| PD ER+ (n=9) | 8 | 6 | 8 | 5 | 5 | 8 | |
| PD ER- (n=14) | 8 | 11 | 12 | 11 | 13 | 8 | |
Statistical analysis showed a significant increase (P<0.05) in serum HER-2/neu in the PD(ER+) group and no significant changes in serum EGFR. In the PD(ER-) cohort a significant increase in HER-2/neu between pre-treatment and progression (P<0.05) and between 6 weeks and progression (P<0.05) was evident. PD(ER-) EGFR levels showed a significant decrease between pre-treatment and 6 weeks (P<0.05) and between pre-treatment and progression (P<0.05). In the CB cohort no significant changes in serum EGFR or HER-2/neu were observed and levels remained stable throughout disease.
Conclusions: In the PD cohort an increase in serum HER-2/neu is an indicator of disease progression in both ER+ and ER- patients. EGFR levels were only an indicator of disease progression in the ER- patients of the PD group. This therefore suggests that EGFR is additive to HER-2/neu in predicting therapeutic response and disease outcome in ER- patients of the PD subpopulation of breast cancer patients.
Friday, December 15, 2006 7:00 AM
Poster Session II: Prognosis and Response Prediction: Prognostic Factors I (7:00 AM-9:00 AM)