Serum epidermal growth factor receptor/HER-2 predicts poor survival in patients with metastatic breast cancer.
BACKGROUND
Epidermal growth factor receptor (EGFR, HER-1, and erbB1) is overexpressed in primary breast cancer and had been identified as a poor prognostic factor.


METHODS
Pretreatment serum EGFR levels were quantified by using an enzyme-linked immunoadsorbent assay in a Phase III first-line trial of letrozole and tamoxifen and were correlated with patient outcomes.


RESULTS
Serum EGFR levels in a control group of 117 healthy, postmenopausal women measured 64.1 +/- 13.3 ng/mL (mean +/- standard deviation). Using a cutoff EGFR level of 44.1 ng/mL from the control group (5% nonparametric method), 53 of 535 patients (10%) had decreased serum levels of EGFR. Patients with decreased serum EGFR had no significant difference in objective response rate (ORR), clinical benefit rate (CBR), time to progression (TTP), or time to treatment failure (TTF); however, they did have significantly reduced survival compared with patients who had normal serum EGFR levels (median survival, 23.3 months vs. 30.9 months; P = .007). A combined analysis of pretreatment serum EGFR and HER-2 yielded no additional predictive information for ORR, CBR, TTP, or TTF compared to serum HER-2 alone. However, in the current analysis, a subgroup of patients who had decreased serum EGFR and normal serum HER-2 was identified (n = 39 of 535 patients; 7.3%) that had significantly reduced survival compared with patients who had normal serum levels of both EGFR and HER-2 (median survival, 23.5 months vs. 37.1 months; P = .005). In multivariate analysis, a decreased serum EGFR level remained a significant independent prognostic factor for decreased survival (hazards ratio, 1.58; P = .007).


CONCLUSIONS
In patients who had metastatic breast cancer, decreased serum EGFR/normal serum HER-2 predicted shorter survival compared with patients who had normal levels of serum EGFR/HER-2. This patient subgroup deserves further study to assess their response to and selection for anti-EGFR-directed therapies.
Souder
Christopher
C
Department of Hematology/Oncology, Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033, USA.
Leitzel
Kim
K
Ali
Suhail M
SM
Demers
Laurence
L
Evans
Dean B
DB
Chaudri-Ross
Hilary A
HA
Hackl
Wolfgang
W
Hamer
Peter
P
Carney
Walter
W
Lipton
Allan
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D002277:Carcinoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality*; D004311:Double-Blind Method; D066246:ErbB Receptors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy; D009570:Nitriles / Q000627:therapeutic use; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; D014230:Triazoles